Nuclear processes involving the weak interaction can be used to extract information on some elusive properties of particles. Remarkably useful to this goal is parity-violating elastic electron ...scattering off nuclei, which can be used to determine accurately the distribution of neutrons within the nucleus, including information on the neutron skin that can be related to the structure of neutron stars. It can also be used to determine the content of strange quark-antiquark virtual pairs in nucleons and can help in evaluating accurately Standard Model parameters or higher-order radiative corrections. To achieve these goals it is essential keeping under control the theoretical uncertainties that arise in modelling some confounding nuclear effects, such as isospin mixing or Coulomb distortion of electron wave functions. The paradigm of an evasive particle in current physics is dark matter. Sterile neutrinos are hypothetical dark matter candidates that could be produced in nuclear beta decays leaving a signal in the energy spectrum of the emitted charged lepton. They can also be coherently scattered by nuclei through an indirect weak neutral interaction, whose cross section can be written in terms of elastic electron scattering observables. We study the probability of these production and detection mechanisms using experimental and cosmological constraints on the sterile neutrino properties. The coherent scattering cross section off nuclei has also been analyzed for the Standard Model neutrinos, being a notably elusive process that has been recently measured for the first time and that can be used for Standard Model tests or for nuclear structure studies in ways analogous to parity-violating electron scattering.
Despite important breakthroughs in bottom‐up synthetic biology, a major challenge still remains the construction of free‐standing, macroscopic, and robust materials from protocell building blocks ...that are stable in water and capable of emergent behaviors. Herein, a new floating mold technique for the fabrication of millimeter‐ to centimeter‐sized protocellular materials (PCMs) of any shape that overcomes most of the current challenges in prototissue engineering is reported. Significantly, this technique also allows for the generation of 2D periodic arrays of PCMs that display an emergent non‐equilibrium spatiotemporal sensing behavior. These arrays are capable of collectively translating the information provided by the external environment and are encoded in the form of propagating reaction–diffusion fronts into a readable dynamic signal output. Overall, the methodology opens up a route to the fabrication of macroscopic and robust tissue‐like materials with emergent behaviors, providing a new paradigm of bottom‐up synthetic biology and biomimetic materials science.
Protocellular materials are constructed using a bottom‐up strategy enabled by simple floating molds. The technique allows the fabrication of free‐standing, macroscopic, and robust materials from protocell building blocks that are stable in water media, are capable of communicating both internally and with the external environment, and display rudimentary forms of emergent behaviors that are generated from the synergistic interaction of their constituent parts.
Chronic inflammatory diseases are triggered by causal stimuli that might occur long before the appearance of the symptoms. Increasing evidence suggests that these stimuli are necessary but not always ...sufficient to induce the diseases. The murine model of type II collagen emulsified in Freund's incomplete adjuvant (collagen‐induced arthritis) to induce rheumatoid arthritis (RA) follows this pattern as some animals do not develop the chronically inflamed phenotype. Considering that in the immune–pineal axis (IPA) theory adrenal–pineal cross‐talk adjusts early phases of inflammatory processes, we investigated whether differences in IPA activation could explain why some animals are resistant (RES) while others develop RA. We observed a similar increase in 6‐sulfatoxymelatonin (aMT6s) excretion from day 3 to 13 in both RES and RA animals, followed by a significant decrease in RA animals. This pattern of aMT6s excretion positively correlated with plasma corticosterone (CORT) in RES animals. Additionally, RA animals presented a lower aMT6s/CORT ratio than saline‐injected or RES animals. Plasmatic levels of tumour necrosis factor were similar in both groups, but interleukin (IL)‐1β and monocyte chemotactic protein 1 (MCP‐1) levels were lower in RES compared to RA animals. IL‐2 and IL‐4 were decreased in RES animals compared to saline‐injected animals. The aMT6s/CORT ratio inversely correlated with the paw thickness and the inflammatory score (levels of IL‐1β, MCP‐1, IL‐2 and IL‐4 combined). Thus, adrenocortical–pineal positive interaction is an early defence mechanism for avoiding inflammatory chronification.
Key points
Immune–pineal axis imbalance is observed in early‐phase rheumatoid arthritis development.
Only resistant animals present a positive association between adrenal and pineal hormones.
The 6‐sulfatoxymelatonin/corticosterone ratio is decreased in animals that develop rheumatoid arthritis.
The inflammatory score combining the levels of nocturnal interleukin (IL)‐1β, monocyte chemotactic protein 1, IL‐2 and IL‐4 presents a very strong positive correlation with the size of inflammatory lesion.
The 6‐sulfatoxymelatonin/corticosterone ratio presents a strong negative correlation with the inflammatory score and paw oedema size.
figure legend Adrenal–pineal crosstalk provides resistance to RA development in rats. Left, resistance: moderately increased CORT levels lead to glucocorticoid receptor stimulation in the pineal gland, counteracting TNF inhibitory effect and potentiating β1‐adrenoreceptor‐induced pineal melatonin production. Increased melatonin levels associated with corticosterone reduce cellular migration, regulating an appropriate synovial cellular infiltration and the synthesis of cytokines composing the inflammatory score. Right, rheumatoid arthritis: highly elevated corticosterone levels combined with β1‐ + α1‐adrenoceptor activation and circulating TNF reduces the synthesis of melatonin by the pineal gland. Lower circulating melatonin levels lead to increased synovial cellular infiltration. Infiltrated cells, resident fibroblasts and resident macrophages produce large amounts of inflammatory factors, leading to chronic inflammation. The data provide evidence that an unbalanced immune–pineal axis activation lies at the point of origin of RA development (Markus et al. 2021). Figure produced with BioRender.com.
Calcium hexaluminate (CA6) forms a broad range of solid solutions by substitution of Al
3+
with other cations such as, for example, Fe, Co, Mn, etc. Solid solutions of CA6 with magnetic ions have ...attracted interest because they allow designing the magnetic behavior depending on the composition of each solid solution. In this paper, we have studied materials pertaining to an area of the CaO–Al
2
O
3
–Fe
2
O
3
ternary phase diagram that is potentially interesting, but which has not been too much explored so far. We report on various synthesis methods of calcium hexaluminate with iron in solid solution. The percentages of iron introduced have been varied in order to determine the maximum percentage of iron that can enter into solid solution in the calcium hexaluminate such that the materials obtained exhibit magnetic behavior.
Graphical Abstract
Exploring the limits of Fe
3+
solid solution in calcium hexaluminate.
The design and synthesis of a novel acid‐degradable polyethylene glycol‐based N‐hydroxysuccinimide (NHS) ester‐activated crosslinker is reported. The crosslinker is reactive towards nucleophiles and ...features a central ketal functional group that is stable at pH > 7.5 and rapidly hydrolyses at pH > 6.0. The crosslinker is used to (i) fabricate acid‐degradable polysaccharide hydrogels that exhibit controlled degradation upon exposure to an acidic environment or via endogenous enzyme activity; and (ii) construct hydrogel‐filled protein‐polymer microcompartments (termed proteinosomes) capable of pH‐dependent membrane disassembly. Taken together the results provide new opportunities for the fabrication of pH‐responsive soft materials with potential applications in drug delivery, tissue engineering, and soft‐matter bioengineering.
A novel acid‐degradable N‐hydroxysuccinimide (NHS) ester‐activated crosslinker that is stable at pH > 7.5 and rapidly hydrolyses at pH < 6.0 is synthesized and used to fabricate polysaccharide hydrogels that exhibit controlled degradation upon exposure to an acidic environment or via endogenous enzyme activity. The same crosslinker is also used to construct hydrogel‐filled protein‐polymer microcompartments (proteinosomes) capable of pH‐dependent membrane disassembly.
Y chromosomal short tandem repeats (Y-STRs) are used in forensic investigations as a useful complementary tool to autosomal markers. The ongoing development of new kits with an increasing number of ...markers makes it necessary to update populations typed in the Y-STR Haplotype Reference Database to reach at least 23 Y-STRs. A novel Y-STR multiplex panel was developed to offer a cost-efficient alternative to update Y-STR haplotypes from 12 to 23 loci. This panel includes the eleven markers, DYS448, DYS456, DYS458, DYS635, Y-GATA H4, DYS576, DYS481, DYS549, DYS533, DYS570 and DYS643, as well as DYS385a/b for traceability purpose. Developmental validation of this panel was conducted following the recommendations of the Scientific Working Group on DNA Analysis Methods (SWGDAM), showing high sensitivity, tolerance to common inhibitors as well as high species specificity. It was efficient for degraded DNA samples and for detection of male mixtures. When applying it for extending the current data of the Ibiza population, both the discrimination capacity and the haplotype diversity increased from 0.5952 to 0.9048 and from 0.9808 to 0.9977, respectively. Together, the study demonstrates the suitability of this panel in forensic casework.
Immune‐pineal axis activation is part of the assembly of immune responses. Proinflammatory cytokines inhibit the pineal synthesis of melatonin while inducing it in macrophages by mechanisms dependent ...on nuclear factor‐κB (NF‐κB) activation. Cytokines activating the Janus kinase/signal transducer and activator of transcription (STAT) pathways, such as interferon‐gamma (IFN‐γ) and interleukin‐10 (IL‐10), modulate melatonin synthesis in the pineal, bone marrow (BM), and spleen. The stimulatory effect of IFN‐γ upon the pineal gland depends on STAT1/NF‐κB interaction, but the mechanisms controlling IL‐10 effects on melatonin synthesis remain unclear. Here, we evaluated the role of STAT3 and NF‐κB activation by IL‐10 upon the melatonin synthesis of rats' pineal gland, BM, spleen, and peritoneal cells. The results show that IL‐10‐induced interaction of (p)STAT3 with specific NF‐κB dimmers leads to different cell effects. IL‐10 increases the pineal's acetylserotonin O‐methyltransferase (ASMT), N‐acetylserotonin, and melatonin content via nuclear translocation of NF‐κB/STAT3. In BM, the nuclear translocation of STAT3/p65‐NF‐κB complexes increases ASMT expression and melatonin content. Increased pSTAT3/p65‐NF‐κB nuclear translocation in the spleen enhances phosphorylated serotonin N‐acetyltransferase ((p)SNAT) expression and melatonin content. Conversely, in peritoneal cells, IL‐10 leads to NF‐κB p50/p50 inhibitory dimmer nuclear translocation, decreasing (p)SNAT expression and melatonin content. In conclusion, IL‐10's effects on melatonin production depend on the NF‐κB subunits interacting with (p)STAT3. Thus, variations of IL‐10 levels and downstream pathways during immune responses might be critical regulatory factors adjusting pineal and extra‐pineal synthesis of melatonin.
There has been recent interest in low energy, high luminosity polarized electron beams for studies of parity-violating (PV) electron scattering, such as the MESA accelerator at Mainz or an upgraded ...FEL facility at Jefferson Lab. Accurate measurements of the PV asymmetry in elastic electron scattering from nuclei can be used to determine Standard Model couplings, such as the weak-mixing angle or higher-order radiative corrections, as well as to extract specific information on the nuclear and nucleon structure. To this end, low uncertainties are required from modelling some confounding nuclear and nuclear structure effects, including isospin mixing, nucleon strangeness content or Coulomb distortion of electron wave functions. We estimate the sizes and theoretical uncertainties of such effects for a carbon 12 target. An experimental precision in the PV asymmetry of a few tenths of a percent may be reachable under certain kinematic conditions, that are also discussed for the same nuclear target. This high precision PV asymmetry in elastic electron scattering can also be used to relate in a very simple manner the elastic electron-nucleus scattering cross section with the elastic neutrino-nucleus cross section. This novel relationship allows us to exploit experimentally well-determined quantities to predict unknown or recently measured observables, such as coherent neutrino-nucleus cross sections. This idea can be extended to link electron scattering to an even more uncertain magnitude: the direct detection rate of hypothetical weak-interacting dark matter particles through axial and/or vector elastic interactions with nuclei.
Summary
Background
Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology.
Aim
To identify possible environmental and hormonal factors ...related to FFA.
Methods
We conducted a multicentre case–control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease.
Results
For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06–2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06–2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11–2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05–2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07–3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11–23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11–2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7–80.9) or antiageing creams (OR = 1.84; 95% CI 1.04–3.23).
Conclusions
FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.
Summary
Background
Androgenic treatment of female‐to‐male transgender patients may result in androgenetic alopecia (AGA). Use of 5‐alpha‐reductase inhibitors are useful as oral treatment of AA in ...men. There are no previous studies of the use of finasteride in transgender men as treatment of AGA.
Aim
To evaluate the effectiveness and safety of an oral 5α‐reductase inhibitor (finasteride) for AA developed in transgender men.
Methods
This single‐centre retrospective study enrolled female‐to‐male transgender patients with a clinical diagnosis of AGA to receive 1 mg of an oral type II 5α‐reductase inhibitor for at least 12 months.
Results
In all, 10 patients were included in the study. All the patients received a clinical diagnosis of male‐pattern AGA, with 90% classified as stage IV on the Norwood‐Hamilton scale. Mean onset of AGA was 3.25 years after the introduction of androgenic treatment, and 70% of the patients had a family history of AGA. All the patients improved one grade on the Norwood–Hamilton scale after a mean of 5.5 months (range 4–6 months) since the start of finasteride treatment. Two patients stopped treatment for economic reasons and one stopped due to dyspepsia. No sexual or other adverse effects were observed. Patients were given periodic physical and analytical examinations by endocrinologists without any significant finding. Mean follow‐up of patients was 16.2 months.
Conclusion
AA in transgender men has a delayed onset, and is clinically and therapeutically similar to the common male‐pattern‐AGA in cis‐gender men.
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