Miracle-dz/UniFAR-FTUs huggingface dataset:
Studying sperm motility in marine fish: an overview on the state of the art

Summary This contribution reviews existing literature and some new own findings on teleost sperm motility and factors controlling it, emphasizing selected marine species. In marine teleosts with external fertilization (halibut, turbot, sea bass, hake, cod and tuna serving as examples), mainly the osmolality controls sperm motility: movement is activated by transfer from the seminal fluid into sea water, representing a large upward step in osmolality. The exception are flatfishes (such as halibut or turbot) where CO2 is responsible for flagellar immotility in seminal fluid. In all cases, the duration of motility is short and limited to minutes ranges due to partial exhaustion of the ATP energy and to increase of internal ionic concentration as suggested by studies with de-membranated/ATP reactivated flagellae. In this overview, we compare motility characteristics (percentage of active spermatozoa, velocity, linearity), flagellar waves parameters (wave length and amplitude, number of waves) and energy content (respiration and ATP concentration) within species where these data have been established. All parameters show a rapid decrease after activation; therefore progressive forward movement needed by the sperm to effectively reach the egg surface, is limited to a short initial period following activation. In two species (turbot and sea bass) the rapid decrease of sperm motility is reflected by a corresponding decrease of the fertilizing ability. Exposure to external environments (sea water) at activation also leads to local defects of the sperm flagella posing additional limitations on motility duration. However, minor flagellar damages as well as energetic exhaustion are reversible: after a resting period in a non-swimming solution at the end of the motility period, spermatozoa can be re-activated for a second motility period. From these results and from additional data obtained from de-membranated/ATP re-activated spermatozoa, a paradigm has been developed which establishes a link between external osmolality (sea water), internal ionic concentration and control of axonemal activity.
A Descriptive Cross-Sectional Study of Manipulative Dexterity on Different Subtypes of Multiple Sclerosis

Background Manipulative dexterity impairments affect 76% of individuals with multiple sclerosis (MS). Patients with MS can experience reduced skill when performing both basic activities of daily living and instrumental activities of daily living. Many studies consider that physical rehabilitation leads to a decrease in the level of disability, especially at the mild and moderate stages of the disease. However, most studies fail to distinguish between the different MS subtypes. Purpose Our aims were (1) to describe the manipulative skills of people according to the different subtypes of MS, (2) to analyze the correlation between dexterity and self-perception variables, and (3) to identify possible predictors of functionality. Study Design. A descriptive cross-sectional study. Methods 30 individuals with MS. The measurement tools used were the ABILHAND, the Purdue Pegboard Test (PPT), the Nine-Hole Peg Test, and the Box and Block Test. Results All subtypes of MS obtained lower scores for manipulative dexterity compared to normal skill levels, with individuals with primary progressive MS displaying the lowest values. However, the analysis of differences between the different subtypes did not reveal statistically significant intragroup differences. In addition, differences were found regarding the effect size of practically all the variables analyzed for both manipulative dexterity (PPT, NHPT, and BBT) and the self-perception of ADLs (ABILHAND), for which high values (dr = 0.72) and very high values (dr = 1.46) were obtained. Conclusions Although no significant differences were found between the different types of MS, the assessment of manual dexterity and perceived efficacy of daily activities must be considered as prognostic factors in the progression of the disease. These findings may help support further research on targeted interventions to improve dexterity deficiencies, as well as promote an improved quality of therapeutic interventions.
α-Secretase Activation – An Approach to Alzheimer’s Disease Therapy

The nonamyloidogenic pathway of processing the amyloid precursor protein (APP) involves the cleavage within the amyloid-β peptide sequence, and thus precludes amyloid-β formation. The identification of a member of the disintegrin and metalloproteinase family, ADAM10, as an α-secretase that prevents plaque formation and hippocampal deficits in vivo gave us the possibility to examine the α-secretase as a potential target for the therapy of Alzheimer’s disease. Within the priority program Cellular Mechanisms of Alzheimer’s Disease, we investigated several approaches to stimulate the α-secretase pathway. Two protein convertases were found to be responsible for the removal of the prodomain, and for the formation of the mature enzyme with α-secretase activity. The cloning and characterization of the human ADAM10 promoter provided the basis to examine ADAM10 gene expression. We found a common upregulation of ADAM10, APP, and APP-like protein 2 during differentiation of neuronal cells by retinoic acid, and increased α-secretase cleavage of the two substrates. Other approaches for enhancing α-secretase activity are the reduction of cellular cholesterol and the stimulation of G protein-coupled neuropeptide receptors. Our results suggest medications and dietary regiments which enhance the nonamyloidogenic pathway of APP processing to be a valuable approach to Alzheimer’s disease therapy.
Why is SARS-CoV-2 infection milder among children?

Acute respiratory viral diseases, like most other infectious diseases, affect mainly infants and young children, who present with 6-8 episodes per year and usually develop more severe manifestations than in adults. It is well-documented that innate antiviral immune responses in early life are characterized by lower type I interferon (IFN) responses () and reduced natural killer cell activity, which despite their higher numbers exhibit lower cytotoxic capacity and reduced number of cytoplasmic granules and degranulation ability (). Additionally, lower cytotoxic [. ]
Systemic lupus erythematosus and glycation process

Systemic lupus erythematosus (SLE) is a disease of unclear causes, which leads to major immunological disorders. It is characterized by an abnormal immune system activity resulting in the production of autoantibodies. In patients, antibodies targeting normal nuclear components, double-stranded DNA (dsDNA), and phospholipids (cardiolipin) can be detected. The inflammatory process occurs in various tissues and organs, damaging their functions and structure. Disease’s course includes stages of acute symptoms and remissions, and there is no known cure. Pathogenesis and biochemical pathways accompanying systemic lupus erythematosus are widely studied, as existing medication can only bring temporary relief to patients. The recent findings suggest that occurrence of SLE depends on interactions between genetic background of the disease and environmental risk factors such as exposure to tobacco smoke, chemical factors, and hormonal therapy. In the addition, chronic inflammation accompanying SLE disturbs oxidative/antioxidative balance. These processes are linked to intensified advanced glycation end products (AGEs) formation, thus level of AGEs themselves and their receptors (RAGE, sRAGE) are gaining researches attention.
Physical mapping of rDNA genes establishes the karyotype of almond

The localisation of ribosomal RNA genes on chromosomes of almond (Prunus amygdalus, 2n = 16) was studied by fluorescence in situ hybridisation. Simultaneous double-colour hybridisation with both 18S-5.8S-25S and 5S rDNA probes demonstrated that all chromosomes can be identified. In spite of the small size, differences in length between chromosomes that hybridised with the same rDNA probe as well as between chromosomes without hybridisation signal are apparent. Chromosomes were ordered in the karyotype according to their length. The 18S-5.8S-25S rDNA genes were detected in subdistal positions of chromosomes 2, 3, and 8. Sites located on chromosomes 2 and 3 carry a higher number of repeats than the site of chromosome 8. The 5S rDNA genes were found proximally located on chromosomes 5 and 7, the signal on chromosome 5 showing higher intensity than the signal on chromosome 7. Chromosomes 1, 4, and 6 show no hybridisation signal.
Widespread loss of Caribbean acroporid corals was underway before coral bleaching and disease outbreaks

Endangered staghorn and elkhorn corals began disappearing from Caribbean reefs decades before climate change impacts. The mass mortality of acroporid corals has transformed Caribbean reefs from coral- to macroalgal-dominated habitats since systematic monitoring began in the 1970s. Declines have been attributed to overfishing, pollution, sea urchin and coral disease, and climate change, but the mechanisms are unresolved due to the dearth of pre-1970s data. We used paleoecological, historical, and survey data to track Acropora presence and dominance throughout the Caribbean from the prehuman period to present. Declines in dominance from prehuman values first occurred in the 1950s for Acropora palmata and the 1960s for Acropora cervicornis, decades before outbreaks of acroporid disease or bleaching. We compared trends in Acropora dominance since 1950 to potential regional and local drivers. Human population negatively affected and consumption of fertilizer for agriculture positively affected A. palmata dominance, the latter likely due to lower human presence in agricultural areas. The earlier, local roots of Caribbean Acropora declines highlight the urgency of mitigating local human impacts.
Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates

Machine learning–based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys. Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)–rich protein aggregates [termed “Lewy bodies” (LBs)], is a well-established characteristic of Parkinson’s disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning–based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.
Multiple-delayed release formulation approach for the treatment of methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequent nosocomial pathogens in developed countries. Although several novel antibacterial agents possessing novel mode of action have been developed to date, the continuous effort to investigate an effective combination of front-line drugs is considered important in anti-MRSA drug development. The combination chemotherapy with front-line drugs is expected to provide effective, safe, and less expensive treatment. Oral trimethoprim/sulfamethoxazole combination therapy has been utilized for treatment of several nosocomical infections. Importantly, no antagonism has been reported for combinations of trimethoprim with many other front-line antibiotics. MiddleBrook Pharmaceuticals has developed the pulsatile delivery systems of three to four different antibacterial agents, including trimethoprim and sulfamethoxazole, for the treatment of MRSA infections. The liberation of individual drugs theoretically follows a programmable lag phase (no release) from the time of administration. Pulsatile drug delivery system provides optimal release profiles for a combination of drugs. The clinical data that would be obtained based on these claims are expected to be of significance in terms of developing combination chemotherapy for MRSA infections via a pulsatile drug release control system.
An Interpretive Description of Women’s Experience in Coordinated, Multidisciplinary Treatment for an Eating Disorder

Coordinated, multidisciplinary treatment for women with eating disorders is consistently recommended as maximally effective, but few studies have considered the patient experience. This qualitative study examined the experiences of women receiving such care in an outpatient setting. Using an interpretive description methodology, we conducted 12 in-depth interviews with participants who were diagnosed with an eating disorder and were receiving team-based treatment. Patients uniformly advocated for the coordinated, multidisciplinary treatment approach. Analysis of participants’ experiences yielded four categories: relying on the lifeline of communication, supporting autonomy, drawing on individual strengths, and valuing synergy. These findings build on previous research emphasizing the importance of autonomy support and connectedness in the recovery process from an eating disorder. Findings highlight the importance of nurses to support a multidisciplinary care approach to working with this patient population; these women’s voices also support a treatment approach that, despite being widely recommended, is vastly understudied and underutilized.
Advanced late-onset retinitis pigmentosa with dominant-acting D477G RPE65 mutation is responsive to oral synthetic retinoid therapy

Objectives No therapeutic interventions are currently available for autosomal dominant retinitis pigmentosa (adRP). An RPE65 Asp477Gly transition associates with late-onset adRP, reduced RPE65 enzymatic activity being one feature associated with this dominant variant. Our objective: to assess whether in a proof-of-concept study, oral synthetic 9 cis-retinyl acetate therapy improves vision in such advanced disease. Methods and analysis A phase 1b proof-of-concept clinical trial was conducted involving five patients with advanced disease, aged 41–68 years. Goldmann visual fields (GVF) and visual acuities (VA) were assessed for 6–12 months after 7-day treatment, patients receiving consecutive oral doses (40 mg/m2) of 9-cis-retinyl acetate, a synthetic retinoid replacement. Results Pathological effects of D477G variant were preliminarily assessed by electroretinography in mice expressing AAV-delivered D477G RPE65, by MTS [3-(4,5-dimethylthiazol-2-yl)−5-(3-carboxyme- thoxyphenyl)−2-(4-sulfophenyl)−2H-tetrazolium] assays on RPE viability and enzyme activity in cultured cells. In addition to a mild dominant effect reflected in reduced electroretinographics in mice, and reduced cellular function in vitro, D477G exhibited reduced enzymatic RPE65 activity in vitro. In patients, significant improvements were observed in GVF from baseline ranging from 70% to 200% in three of five subjects aged 67–68 years, with largest improvements at 7–10 months. Of two GVF non-responders, one had significant visual acuity improvement (5–15 letters) from baseline after 6 months. Conclusion Families with D477G variant have been identified in Ireland, the UK, France, the USA and Canada. Effects of single 7-day oral retinoid supplementation lasted at least 6 months, possibly giving visual benefit throughout remaining life in patients with advanced disease, where gene therapy is unlikely to prove beneficial.
Germline and soma: interactions during early mouse development

Abstract Mouse germ cells during their migratory period depend for their survival, proliferation and guidance on growth factors and/or extracellular matrix produced by somatic tissue. The somatic development of the ovary appears more affected by the absence of germ cells than is the testis. Some factor emanating from testicular somatic tissue, probably from Sertoli cells, inhibits germ cells from entering meiosis before birth and thus induces them to embark on spermatogenesis rather than oogenesis. Genomic imprinting must also reflect some somatic influence.
Drought-induced nitrogen retranslocation in perennial C4 grasses of tallgrass prairie

We determined if drought-induced nitrogen retranslocation occurs in pe- rennial grasses of tallgrass prairie, as suggested from studies of annual changes in plant N content. To test this, we analyzed six C4 grasses representing a wide range of drought tolerance for shoot, rhizome, and root N before and after controlled drought. Shoot N concentration decreased in all species during drought (31-41%), including in recently ex- panded leaves (23-38%). No consistent pattern with respect to drought tolerance was apparent in these decreases or in observed changes in distribution of whole-plant N, al- though there was some suggestion of a mesic-to-xeric gradient in the magnitude ofretranslo- cation. For example, the proportion of total plant N allocated to shoots decreased during drought 20-29% in the most mesic species over three experiments, 2-12% in the three intermediate species, and 4-6% in the two most xeric species, for pre- vs. post-drought comparisons. However, when drought-stressed plants were compared to well-watered age controls, the respective values were 20-21%, 12-20%, and 0-19%, the apparent result of size-related changes in N allocation in control plants in one experiment. In most cases, shoot N was moved primarily into rhizomes, though in one species with intermediate drought tolerance, evidence suggested that much of the retranslocated shoot N was ap- parently lost through fine-root turnover. Retranslocation of shoot N to rhizomes and roots, confirmed by monitoring movement of 35S-methionine, was in response to drought stress rather than phenology and involved the entire shoot (e.g., blades, culms, recently expanded leaves). Post-drought photosynthesis and leaf N concentration remained well below pre- drought levels 6 d following rewatering. Thus decreases in leaf N status during drought as a consequence of retranslocation likely result in lower photosynthetic capacity and de- creased whole-plant carbon gain following relief of water stress after rain. Drought-induced retranslocation may serve to protect plant N from loss to herbivory, fire, and volatilization during periods when soil N uptake and carbon assimilation are limited by water availability.
Dlp-mediated Hh and Wnt signaling interdependence is critical in the niche for germline stem cell progeny differentiation

Proteoglycan-mediated Hh and Wnt signaling interdependence is required in the niche for stem cell progeny differentiation. Although multiple signaling pathways work synergistically in various niches to control stem cell self-renewal and differentiation, it remains poorly understood how they cooperate with one another molecularly. In the Drosophila ovary, Hh and Wnt pathways function in the niche to promote germline stem cell (GSC) progeny differentiation. Here, we show that glypican Dlp-mediated Hh and Wnt signaling interdependence operates in the niche to promote GSC progeny differentiation by preventing BMP signaling. Hh/Wnt-mediated dlp repression is essential for their signaling interdependence in niche cells and for GSC progeny differentiation by preventing BMP signaling. Mechanistically, Hh and Wnt downstream transcription factors directly bind to the same dlp regulatory region and recruit corepressors composed of transcription factor Croc and Egg/H3K9 trimethylase to repress Dlp expression. Therefore, our study reveals a novel mechanism for Hh/Wnt signaling–mediated direct dlp repression and a novel regulatory mechanism for Dlp-mediated Hh/Wnt signaling interdependence in the GSC differentiation niche.
Changes in intraocular pressure, horizontal pupil diameter, and tear production during the use of topical 1% cyclopentolate in cats and rabbits

Background: Cyclopentolate is not commonly used as mydriatic drug in veterinary medicine because of limited data on the local and systemic effects in animals. Aim: To determine the effects of topical 1% cyclopentolate hydrochloride on intraocular pressure (IOP), horizontal pupil diameter (HPD) and tear production in the cat and rabbit’s eye during the first hour and up to 36 hours after treatment. Methods: One drop of 1% cyclopentolate hydrochloride was used in the left eye in 10 clinically and ophthalmologically healthy domestic cats and 10 rabbits. IOP and HPD were recorded every 5 minutes during the first hour, then every 2 hours during the following 12-hour period, and at 24 and 36 hours after application. Schirmer tear test (STT) was measured at 30 and 60 minute after treatment, then in same time points as IOP and HPD. Rebound tonometer (TonoVet®) was used to assess IOP, Jameson calliper to measure HPD and STT to determine the tear production. Results: 1% cyclopentolate increased IOP in cats, reaching a maximum (28.1 ± 5.4 mmHg) at T50 and in rabbits at T25 (16.7 ± 1.3 mmHg). Maximal mydriasis in cats was observed at T40 and lasted 24–36 hours, but in rabbits at T25, and returned to pre-treatment values at T10h–T12h. In cats, STT decreased in both eyes 30 minutes after treatment and remained lower throughout the 36-hour period. In rabbits, STT decreased in the treated eye 30 minutes after treatment, but all following STT measurements returned to normal pre-treatment levels. Conclusion: Study showed novel data about the effects of 1% cyclopentolate to IOP, HPD, STT in cats and rabbits. Cyclopentolate in cats caused mydriasis 20–40 minutes after the treatment by increasing IOP, at the same time, pupil diameter reached pre-treatment values 24–36 hours after treatment. In rabbit’s mydriasis occurred faster, 10–25 minutes after treatment without significant IOP increase and mydriasis lasted 10–12 hours. Significant STT decrease was recorded in cats, but more likely were connected to stress factors. This drug could be considered as a therapeutical alternative in rabbit more than in cats.