Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos

Primary cilia are ubiquitous microtubule-based organelles that serve as signaling hubs for numerous developmental pathways, most notably the Hedgehog (Hh) pathway. Defects in the structure or function of primary cilia result in a class of diseases called ciliopathies. It is well known that primary cilia participate in transducing a Hh signal, and as such ciliopathies frequently present with phenotypes indicative of aberrant Hh function. Interestingly, the exact mechanisms of cilia-dependent Hh signaling transduction are unclear as some ciliopathic animal models simultaneously present with gain-of-Hh phenotypes in one organ system and loss-of-Hh phenotypes in another. To better understand how Hh signaling is perturbed across different tissues in ciliopathic conditions, we examined four distinct Hh-dependent signaling centers in the naturally occurring avian ciliopathic mutant talpid2 (ta2). In addition to the well-known and previously reported limb and craniofacial malformations, we observed dorsal-ventral patterning defects in the neural tube, and a shortened gastrointestinal tract. Molecular analyses for elements of the Hh pathway revealed that the loss of cilia impact transduction of an Hh signal in a tissue-specific manner at variable levels of the pathway. These studies will provide increased knowledge into how impaired ciliogenesis differentially regulates Hh signaling across tissues and will provide potential avenues for future targeted therapeutic treatments.
Evidence of Antimicrobial Resistance and Presence of Pathogenicity Genes in Yersinia enterocolitica Isolate from Wild Boars

Yersinia enterocolitica (Ye) is a very important zoonosis andwild boars play a pivotal role in its transmission. In the last decade, the wild boar population has undergone a strong increase that haspushed them towards urbanized areas, facilitating the human–wildlife interface and the spread of infectious diseases from wildlife to domestic animals and humans. Therefore, it is important to know the serotype, antimicrobial resistance and presence of pathogenicity genes of Yersinia enterocolitica (Ye) isolated in species. From 2013 to 2018, we analyzed the liver of 4890 wild boars hunted in Liguria region; we isolated and serotyped 126 Ye positive samples. A decisive role in the pathogenicity is given by the presence of virulence genes; in Ye isolated we found ystB (~70%), ymoA (45.2%), ail (43.6%) and ystA (~20%). Moreover, we evaluated the susceptibility at various antimicrobic agents (Ampicillin, Chloramphenicol, Enrofloxacin, Gentamicin, Kanamycin, Trimethoprim–Sulfamethoxazole, Sulfisoxazole, Ceftiofur and Tetracycline). The antibiotic resistance was analyzed, and we found a time-dependent increase. It is important to shed light on the role of the wild boars as a reserve of potentially dangerous diseases for humans, and also on the antibiotic resistance that represents a public health problem.
Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28–2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2–307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.
Bone Pain in Multiple Myeloma (BPMM)—A Protocol for a Prospective, Longitudinal, Observational Study

Simple Summary Multiple myeloma is a bone marrow cancer that often causes bone pain, but little is known about the pain characteristics and mechanisms in this condition. This clinical study aims to: 1. characterize the type, location and intensity of pain in myeloma patients, and its effect of quality of life, and 2. investigate whether the nerve fibers in the bone of myeloma patients are altered. We will also explore whether pain intensity is correlated to blood indicators of inflammation or bone damage. Study results will help identify the mechanisms of myeloma-induced bone pain, allowing the development of new analgesics for these patients. Abstract Multiple myeloma (MM) is a bone marrow neoplasia that causes bone pain in 70% patients. While preclinical models of MM have suggested that both nerve sprouting and nerve injury may be causative for the pain, there is a lack of clinical data. Thus, the primary aims of this clinical study are: (1) to provide a deep characterization of the subjective experience of pain and quality of life in MM patients; (2) to investigate disturbances in the bone innervation of MM patients. Secondary aims include exploring correlations between pain and serum inflammatory and bone turnover biomarkers. In a prospective, observational study (clinicaltrials.gov: NCT04273425), patients with suspected MM requiring a diagnostic iliac crest biopsy at Sheffield Teaching Hospital (UK) are invited to participate. Consenting patients answer seven standardized questionnaires assessing pain, quality of life and catastrophizing. Bone turnover biomarkers and inflammatory cytokines are measured in fasting serum samples, and bone innervation is evaluated in diagnostic biopsies. MM patients are invited to a follow-up upon completion of first line treatment. This will be the first deep characterization of pain in MM patients and its correlation with disturbances in bone innervation. Understanding how bone turnover and inflammation correlate to pain in MM is crucial to identify novel analgesic targets for this condition.
Associations between Inter-Limb Asymmetries in Jump and Change of Direction Speed Tests and Physical Performance in Adolescent Female Soccer Players

The association between asymmetries in jump and change of direction (COD) with physical performance in several sports show inconclusive results. The purposes of this study were to: (1) measure inter-limb asymmetries in three distinct groups in adolescent female soccer players and, (2) to determine the association between inter-limb asymmetries and physical performance in different age groups. Fifty-four players were distributed in three age groups: U-18, U-16 and U-14. All of them performed a series of jumps, sprints and change of direction speed tests. Asymmetries were assessed as the percentage difference between limbs, with the equation: 100/Max value (right and left) * in value (right and left) * −1 + 100. Mean inter-limb asymmetries were 2.91%, 4.82% and 11.6% for 180° COD, single leg hop and single leg countermovement jump tests respectively, but higher percentages of asymmetries were observed in many players individually. U-18 and U-16 showed significant differences on 180° left COD compared to U-14. Effect size (ES): 0.80 and 0.74, respectively; U-18 presented differences on single left leg hop test compared to U-14, ES: −0.72; U-16 also showed differences on 40 m speed compared to U-14, ES 0.87 (All p < 0.05). Jumping and COD physical tests show asymmetries in adolescent female soccer players, but these asymmetries do not interfere with physical performance. The largest asymmetry was observed in the single leg countermovement jump, and no asymmetries between groups were found. Due to the high variability in the direction of asymmetries, it is recommended to consider players’ individual asymmetries for designing specific training programs.
Microcapillary Reactors via Coaxial Electrospinning: Fabrication of Small Poly(Acrylic Acid) Gel Beads and Thin Threads of Biological Cell Dimensions

Poly(acrylic acid) (PAA) bulk gels and threads, typically derived via free-radical polymerization, are of interest as anionic polyelectrolyte mimics of cellular cytosol and as models for early protocells. The thread dimensions have been limited by the diameters of readily-available glass or plastic capillaries, and threads with diameters of less than 50 µm have been difficult to achieve. Here, we report a useful approach for achieving crosslinked, partially neutralized PAA, namely poly(acrylate), gel threads with diameters of a few microns when dry. This technique utilizes coaxial electrospinning to effectively produce capillaries (shells) of polystyrene loaded with a gel-forming precursor mixture composed of 3 M acrylic acid, methylene-bisacrylamide, potassium persulfate and 2.2 M NaOH in the core, followed by thermally-induced polymerization and then the removal of the polystyrene shell. Relatively long (up to 5 mm), continuous PAA threads with thicknesses of 5–15 µm are readily obtained, along with a multitude of PAA gel particles, which result from the occasional break-up of the fluid core prior to gel formation during the electrospinning process. The threads and beads are of the sizes of interest to model ancient protocells, certain functional aspects of excitable cells, such as myocytes and neurons, and various membraneless organelles.
Expression of AhATL1, an ABA Transport Factor Gene from Peanut, Is Affected by Altered Memory Gene Expression Patterns and Increased Tolerance to Drought Stress in Arabidopsis

Arachis hypogaea abscisic acid transporter like-1 (AhATL1) modulates abscisic acid (ABA) sensitivity by specifically influencing the importing of ABA into cells, and is a key player in plant stress responses. However, there is limited information on ABA transporters in crops. In this study, we found that the level of AhATL1 expression and AhATL1 distribution increased more rapidly in the second drought (D2) compared with in the first drought (D1). Compared with the first recovery (R1), the AhATL1 expression level and ABA content remained at a higher level during the second recovery (R2). The heterologous overexpression of AhATL1 in Arabidopsis changed the expression pattern of certain memory genes and changed the post response gene type into the memory gene type. Regarding the proline and water content of Col (Arabidopsis thaliana L. Heynh., Col-0), atabcg22, and AhATL1-OX during drought training, the second drought (D2) was more severe than the first drought (D1), which was more conducive to maintaining the cell osmotic balance and resisting drought. In summary, drought stress memory resulted in a rapid increase in the AhATL1 expression and AhATL1 distribution level, and then raised the endogenous ABA content and changed the post response gene type into the memory gene type, which enhanced the drought resistance and recovery ability.
Influence of Different Light Spectrums on Behaviour and Welfare in Laying Hens

Simple Summary This study investigated how different types of lighting affect laying hen behaviour and welfare. Amount and quality of light are important for birds to perform their natural behaviours, e.g., find food and water, recognise conspecifics and safely navigate their environment. The lighting used in poultry production facilities differs considerably from light conditions in the natural environment in which domestic fowl have evolved, which might have negative consequences for their welfare. This study examined whether light closely resembling natural daylight and light found in forest understory in Southeast Asia (ancestral habitat of jungle fowl) affected the behaviour of laying hens. The results revealed that birds had a preference for natural lighting in some situations. It is likely that these effects were due to the presence of ultraviolet light, which is known to be important for visual performance in birds. However, the differences were rather small, indicating that sufficient light intensity and other quality factors in the housing environment are more important in maintaining high welfare than the specific spectral composition of the light. This new knowledge can be used to improve the housing environment of domestic fowl by supplying artificial spectrums replicating natural lighting. Abstract Artificial commercial lighting used in animal production facilities can have negative influences on visual abilities, behaviour and welfare of domestic fowl. This study examined the effects of natural-derived light spectrums on behaviour, production and welfare of laying hens reared from hatching into adulthood. Comparisons were made of frequency of a range of behaviours associated with activity, aggression and comfort in birds kept in control light (commercial standard), daylight (full spectrum, including ultraviolet (UV) wavelengths and forest light (forest understorey, including UV). In addition, bird preferences for different lights, feather damage and egg production were monitored. The results showed that the behavioural repertoire of birds changed with age, while the effects of light treatment were subtle. Some evidence was found that birds preferred either daylight or forest light to control light, suggesting that inclusion of UV contributed to the preference. Daylight and forest light were associated with more active behaviours, and daylight with better plumage and later start of lay. Thus natural-like light may have beneficial effects on domestic fowl, but the differences between broad-spectrum light sources are rather small.
Food Consumption Determinants and Barriers for Healthy Eating at the Workplace—A University Setting

Background: A wide variety of social, cultural and economic factors may influence dietary patterns. This work aims to identify the main determinants of food consumption and barriers for healthy eating at the workplace, in a university setting. Methods: A cross-sectional observational study was conducted with 533 participants. Data were obtained through the application of a self-administered questionnaire that included socio-demographic information, food consumption determinants and the main perceived barriers for healthy eating at the workplace. Results: The respondents identified “price” (22.5%), “meal quality” (20.7%), and “location/distance” (16.5%). For women, the determinant “availability of healthy food options” was more important than for men (p < 0.001). The food consumption determinants at the workplace most referred to by respondents were related to the nutritional value. Smell, taste, appearance and texture, and good value for money, were also considered important for choosing food at the workplace. Respondents referred to work commitments and lack of time as the main barriers for healthy eating at the workplace. Conclusions: Identification of determinants involved in food consumption, and the barriers for healthy eating, may contribute to a better definition of health promotion initiatives at the workplace aiming to improve nutritional intake.
The effects of rootstock on the volatile flavor components of page mandarin (( Citrus reticulata var dancy × Citrus paradisi var dancan) × Citrus clemantina ) flower and leaf

The effects of rootstock on the volatile flavor components of page mandarin flower and leaf were investigated in this study. Flower flavor components were extracted by using ultrasound(US) water bath apparatus and eluted by n-pentane: diethylether(1:2) solvent and then analyzed by GC-FID and GC-MS. Leaf flavor components were extracted by using water distillation method and eluted by using n-hexane solvent and then analyzed by GC-FID and GC-MS. Fifty-two flower components and, sixty-nine leaf components including: aldehydes, alcohols, esters, ketones, monoterpenes, sesquiterpenes and other components were identified and quantified. The major flavor components were linalool, limonene, ocimene, -pinene, sabinene and myrcene. The flower and leaf oil from plants grown on Swingle Citrumelo and Yuzu showed the highest content of aldehydes. Since the aldehyde content of citrus oil is considered one of the more important indicators of high quality, rootstock apparently has a profound influence on Page mandarin flower and leaf oil quality. Key words: Page mandarin flower, page mandarin leaf, flavor components, rootstock, ultrasound, water-distillation
The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’.
Structural Basis for the Function of the C-Terminal Proton Release Pathway in the Calcium Pump

The calcium pump (sarco/endoplasmic reticulum Ca2+-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca2+ during muscle relaxation. Active Ca2+ transport by SERCA involves the structural transition from a low-Ca2+ affinity E2 state toward a high-Ca2+ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca2+ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump.
Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study

Background One-fourth of women experience substantially higher weight years after childbirth. We examined weight change from prepregnancy to 18 months postpartum according to subsequent maternal risk of hypertension and cardiovascular disease (CVD). Methods and findings We conducted a cohort study of 47,966 women with a live-born singleton within the Danish National Birth Cohort (DNBC; 1997–2002). Interviews during pregnancy and 6 and 18 months postpartum provided information on height, gestational weight gain (GWG), postpartum weights, and maternal characteristics. Information on pregnancy complications, incident hypertension, and CVD was obtained from the National Patient Register. Using Cox regression, we estimated adjusted hazard ratios (HRs; 95% confidence interval [CI]) for hypertension and CVD through 16 years of follow-up. During this period, 2,011 women were diagnosed at the hospital with hypertension and 1,321 with CVD. The women were on average 32.3 years old (range 18.0–49.2) at start of follow-up, 73% had a prepregnancy BMI <25, and 27% a prepregnancy BMI ≥25. Compared with a stable weight (±1 BMI unit), weight gains from prepregnancy to 18 months postpartum of >1–2 and >2 BMI units were associated with 25% (10%–42%), P = 0.001 and 31% (14%–52%), P < 0.001 higher risks of hypertension, respectively. These risks were similar whether weight gain presented postpartum weight retention or a new gain from 6 months to 18 months postpartum and whether GWG was below, within, or above the recommendations. For CVD, findings differed according to prepregnancy BMI. In women with normal-/underweight, weight gain >2 BMI units and weight loss >1 BMI unit were associated with 48% (17%–87%), P = 0.001 and 28% (6%–55%), P = 0.01 higher risks of CVD, respectively. Further, weight loss >1 BMI unit combined with a GWG below recommended was associated with a 70% (24%–135%), P = 0.001 higher risk of CVD. No such increased risks were observed among women with overweight/obesity (interaction by prepregnancy BMI, P = 0.01, 0.03, and 0.03, respectively). The limitations of this observational study include potential confounding by prepregnancy metabolic health and self-reported maternal weights, which may lead to some misclassification. Conclusions Postpartum weight retention/new gain in all mothers and postpartum weight loss in mothers with normal-/underweight may be associated with later adverse cardiovascular health.