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Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level. Intrinsically disordered protein polymers can be designed to encode tunable lower or upper critical solution temperatures in physiological solutions.

The skin's barrier arises from proliferative cells that generate a perpetual upward flux of terminally differentiating epidermal cells. Cells nearing the body surface suddenly lose their organelles, becoming dead cellular ghosts called squames. Working in mouse tissue, Garcia Quiroz et al. found that as differentiation-specific proteins accumulate in the keratinocytes, they undergo a vinegar-in-oil type of phase separation that crowds the cytoplasm with increasingly viscous protein droplets (see the Perspective by Rai and Pelkmans). Upon approaching the acidic skin surface, the environmentally sensitive liquid-like droplets respond and dissipate, driving squame formation. These dynamics come into play in human skin barrier diseases, where mutations cause maladapted liquid-phase transitions. Science , this issue p. eaax9554 ; see also p. 1193 Phase-separation sensors reveal abundant liquid-like organelles at the crux of skin barrier formation. At the body surface, skin’s stratified squamous epithelium is challenged by environmental extremes. The surface of the skin is composed of enucleated, flattened surface squames. They derive from underlying, transcriptionally active keratinocytes that display filaggrin-containing keratohyalin granules (KGs) whose function is unclear. Here, we found that filaggrin assembles KGs through liquid-liquid phase separation. The dynamics of phase separation governed terminal differentiation and were disrupted by human skin barrier disease–associated mutations. We used fluorescent sensors to investigate endogenous phase behavior in mice. Phase transitions during epidermal stratification crowded cellular spaces with liquid-like KGs whose coalescence was restricted by keratin filament bundles. We imaged cells as they neared the skin surface and found that environmentally regulated KG phase dynamics drive squame formation. Thus, epidermal structure and function are driven by phase-separation dynamics.

River hydrology shapes the sources, concentration, and stoichiometry of organic matter within drainage basins. However, our understanding of how the microbes process dissolved organic matter (DOM) and recycle nutrients in tropical rivers needs to be improved. This study explores the relationships between elemental DOM composition (carbon/nitrogen/phosphorus: C/N/P), C and N uptake, and C mineralization by autochthonous bacterioplankton in the Usumacinta River, one of the most important fluvial systems in Mexico. Our study investigated changes in the composition and concentration of DOM and evaluated carbon dioxide (CO 2 )production rates (C–CO 2 ) through laboratory experiments. We compared three sites representing the middle and lower river basins, including their transitional zones, during the rainy and dry seasons. After incubation (120 h at 25°C), the DOM decreased between 25% and 89% of C content. Notably, the initial high proportion of C in DOM in samples from the middle–forested zone and the transition led to elevated C–CO 2 rates (>10 mg l −1 day −1 ), in contrast to the lower initial C proportion and subsequent C–CO 2 rates (<7 mg l −1 day −1 ) in the lower river basin. We also found that dissolved organic carbon uptake and NO 3 − and NH 4 + production were higher during the dry season than in the rainy season. The low water flow in the river during the dry season accentuated the differences in elemental composition and microbial processing of DOM among the sites, while the high water flow of the rainy season homogenized these factors. Our findings indicate that microbial metabolism operates with reduced efficiency in C-rich environments like forests, particularly when faced with high C/N and C/P ratios in DOM. This study highlights the influence of the tropical hydrological regime (rainy and dry seasons) and the longitudinal changes in the river basin (middle and lower) topography and land cover on microbial metabolism by constraining DOM characteristics, emphasizing the crucial role of elemental ratios in river DOM processing.

We present new results of the coccolith fluxes in the Perdido and Coatzacoalcos areas of the Gulf of Mexico (GoM) and explore the environmental variables that may control them. The deep-water region of the GoM is known for its oligotrophic, nutrient-limited surface waters, which are relatively isolated from eutrophic waters near the coast; however, it is seasonally affected by nutrient-rich plumes of coastal waters that increase export production. Two sediment trap moorings located at a water depth of 1100 m collected settling particles from June 2016 to July 2017. The Perdido trap collected 47 species of coccoliths, and the Coatzacoalcos trap 56 species throughout the study period. Total coccolith fluxes showed a seasonal response in both trap locations, with lower fluxes during spring and summer, associated with highly stratified water column conditions that were evident in the Coatzacoalcos trap, and higher fluxes during late autumn and winter, associated with deepening mixed layer in response to cooling and to the strong “Nortes” winds. The Perdido trap showed higher total coccolith fluxes with an annual average of 3.1 x 10 9  ± 0.9 x 10 9 coccoliths per m -2 d -1 , than the Coatzacoalcos trap of 1.9 x 10 9  ± 1.1 x 10 9 coccoliths m -2 d -1 . The upper photic zone (mainly, Emiliania huxleyi and Gephyrocapsa oceanica ) showed high fluxes throughout the study period in both traps, reflecting the coastal shelf influence. Overall, three species dominated the composition of the coccolith fluxes in both areas: E. huxleyi , G. oceanica , and Florisphaera profunda , reaching 88% in the Perdido and 84% in the Coatzacoalcos trap. These results suggest that the coccolith export production in the Perdido and Coatzacoalcos traps is strongly influenced by the cooling and deepening of the mixed layer depth during autumn and winter, as well as advection processes between the continental shelf and the offshore region, and multifactorial processes such as loop current mesoscale eddies that affect the GoM.

Sport biomechanics and training have traditionally been tested under laboratory conditions, requiring specific settings and expensive equipment [...].Sport biomechanics and training have traditionally been tested under laboratory conditions, requiring specific settings and expensive equipment [...].

Background S-RNase-based self-incompatibility (SI) occurs in the Solanaceae, Rosaceae and Plantaginaceae. In all three families, compatibility is controlled by a polymorphic S-locus encoding at least two genes. S-RNases determine the specificity of pollen rejection in the pistil, and S-locus F-box proteins fulfill this function in pollen. S-RNases are thought to function as S-specific cytotoxins as well as recognition proteins. Thus, incompatibility results from the cytotoxic activity of S-RNase, while compatible pollen tubes evade S-RNase cytotoxicity. Scope The S-specificity determinants are known, but many questions remain. In this review, the genetics of SI are introduced and the characteristics of S-RNases and pollen F-box proteins are briefly described. A variety of modifier genes also required for SI are also reviewed. Mutations affecting compatibility in pollen are especially important for defining models of compatibility and incompatibility. In Solanaceae, pollen-side mutations causing breakdown in SI have been attributed to the heteroallelic pollen effect, but a mutation in Solanum chacoense may be an exception. This has been interpreted to mean that pollen incompatibility is the default condition unless the S-locus F-box protein confers resistance to S-RNase. In Prunus, however, S-locus F-box protein gene mutations clearly cause compatibility. Conclusions Two alternative mechanisms have been proposed to explain compatibility and incompatibility: compatibility is explained either as a result of either degradation of non-self S-RNase or by its compartmentalization so that it does not have access to the pollen tube cytoplasm. These models are not necessarily mutually exclusive, but each makes different predictions about whether pollen compatibility or incompatibility is the default. As more factors required for SI are identified and characterized, it will be possible to determine the role each process plays in S-RNase-based SI.

Loss of normal tissue architecture is a hallmark of oncogenic transformation 1 . In developing organisms, tissues architectures are sculpted by mechanical forces during morphogenesis 2 . However, the origins and consequences of tissue architecture during tumorigenesis remain elusive. In skin, premalignant basal cell carcinomas form ‘buds’, while invasive squamous cell carcinomas initiate as ‘folds’. Here, using computational modelling, genetic manipulations and biophysical measurements, we identify the biophysical underpinnings and biological consequences of these tumour architectures. Cell proliferation and actomyosin contractility dominate tissue architectures in monolayer, but not multilayer, epithelia. In stratified epidermis, meanwhile, softening and enhanced remodelling of the basement membrane promote tumour budding, while stiffening of the basement membrane promotes folding. Additional key forces stem from the stratification and differentiation of progenitor cells. Tumour-specific suprabasal stiffness gradients are generated as oncogenic lesions progress towards malignancy, which we computationally predict will alter extensile tensions on the tumour basement membrane. The pathophysiologic ramifications of this prediction are profound. Genetically decreasing the stiffness of basement membranes increases membrane tensions in silico and potentiates the progression of invasive squamous cell carcinomas in vivo. Our findings suggest that mechanical forces—exerted from above and below progenitors of multilayered epithelia—function to shape premalignant tumour architectures and influence tumour progression. Mathematical and experimental approaches are used to investigate the mechanical forces that shape the tumour architecture of two different common forms of skin cancer: basal cell carcinomas and invasive squamous cell carcinomas.

Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes ( CHEK2 ), in putative FCCTX candidate genes ( OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.

This study examines the transformative impact of the Special Zones of Social Interest (AEIS-1) implemented in Diadema, São Paulo, in 1994, as an innovative urban policy tool in Brazil. Rooted in the principle of the social function of property established in the 1988 Federal Constitution, the research analyzes the development of social interest housing projects (HISs) led by housing movement associations. The study adopts a mixed-methods approach, combining primary data from local housing associations and the municipal government with geospatial analysis. The results reveal that between 1996 and 2013, over 20 LHISs were successfully established, directly benefiting approximately 2000 low-income families. These projects utilized a self-construction model financed entirely by families, overcoming the lack of public investment. The findings highlight the critical role of housing associations in organizing, planning, and implementing urban housing initiatives. This model not only addressed housing deficits but also fostered community resilience and inclusivity. By demonstrating how grassroots organizations can drive urban transformation, this research underscores the potential of participatory practices in advancing spatial justice and the right to the city. The Diadema case offers valuable insights for cities facing similar challenges, advocating for equitable and democratic urban development strategies.

The creation of species-specific valid tools for pain assessment is essential to recognize pain and determine the requirement and efficacy of analgesic treatments. This study aimed to assess behaviour and investigate the validity and reliability of an acute pain scale in pigs undergoing orchiectomy. Forty-five pigs aged 38±3 days were castrated under local anaesthesia. Behaviour was video-recorded 30 minutes before and intermittently up to 24 hours after castration. Edited footage (before surgery, after surgery before and after rescue analgesia, and 24 hours postoperatively) was analysed twice (one month apart) by one observer who was present during video-recording (in-person researcher) and three blinded observers. Statistical analysis was performed using R software and differences were considered significant when p<0.05. Intra and inter-observer agreement, based on intra-class correlation coefficient, was good or very good between most observers (>0.60), except between observers 1 and 3 (moderate agreement 0.57). The scale was unidimensional according to principal component analysis. The scale showed acceptable item-total Spearman correlation, excellent predictive and concurrent criterion validity (Spearman correlation ≥ 0.85 between the proposed scale versus visual analogue, numerical rating, and simple descriptive scales), internal consistency (Cronbach's α coefficient >0.80 for all items), responsiveness (the pain scores of all items of the scale increased after castration and decreased after intervention analgesia according to Friedman test), and specificity (> 95%). Sensitivity was good or excellent for most of the items. The optimal cut-off point for rescue analgesia was ≥ 6 of 18. Discriminatory ability was excellent for all observers according to the area under the curve (>0.95). The proposed scale is a reliable and valid instrument and may be used clinically and experimentally to assess postoperative acute pain in pigs. The well-defined cut-off point supports the evaluator´s decision to provide or not analgesia.