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Photosynthetic light harvesting exhibits near-unity quantum efficiency. The high efficiency is achieved through a series of energy and charge transfer steps within a network of pigment-containing proteins. Remarkably, high efficiency is conserved across many organisms despite differences in the protein structures and organization that allow each organism to respond to its own biological niche and the stressors within. In this review, we highlight recent progress toward understanding how organisms maintain optimal light-harvesting ability by acclimating to their environment. First, we review the building blocks of photosynthetic light harvesting, energy transfer, and time-resolved spectroscopic techniques. Then, we explore how three classes of photosynthetic organisms—purple bacteria, cyanobacteria, and green plants—optimize their light-harvesting apparatuses to their particular environment. Overall, research has shown that photosynthetic energy transfer is robust to changing environmental conditions, with each organism utilizing its own strategies to optimize photon capture in its particular biological niche.

Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30–40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.

Plants protect themselves against photodamage from excess energy using a process known as non-photochemical quenching (NPQ). A significant fraction of NPQ is induced by a ΔpH across the membrane, which changes the conformation, composition, and organization of the antenna complexes. In particular, clustering of the major light-harvesting complex (LHCII) has been observed, yet the thermodynamic driving force behind this reorganization has not been determined, largely because measurements of membrane protein interaction energies have not been possible. Here, we introduce a method to quantify membrane protein interaction energies and its application to the thermodynamics of LHCII clusters. By combining single-molecule measurements of LHCII-proteoliposomes at different protein densities and a rigorous analysis of LHCII clusters and photophysics, we quantified the LHCII-LHCII interaction energy to be approximately -5kBTat neutral pH and at least -7kBTat acidic pH. From these values, we found the thermodynamic driving force for LHCII clustering was dominated by these enthalpic contributions. Collectively, this work captures the membrane protein-protein interactions responsible for LHCII clustering from the perspective of equilibrium statistical thermodynamics, which has a long and rich tradition in biology.

The structure, dynamics, and binding of individual biomolecules have been extensively investigated using single-molecule Förster resonance energy transfer (smFRET) as a ‘spectroscopic ruler.’ The FRET efficiency between a fluorophore pair is used to measure distances in the several nanometer range. Existing approaches to detect closer distances come at the expense of sensitivity to longer distances. Here, we introduce single-molecule acceptor rise-time (smART) FRET that spans closer and longer distances. The acceptor rise time encodes the FRET rate, which scales polynomially with distance and thus has a steep dependence that expands the working range by 50%. High precision and accuracy is achieved through the spectroscopic separation between the rise time and the photophysical fluctuations that obfuscate other FRET readouts. Using the nanoscale sensitivity, we resolved the architectures of DNA bound to the single-stranded binding protein fromE. coli, demonstrating the ability of smART FRET to elucidate the complex behaviors of biomolecules.

Loss of function variants in JARID2 were recently reported in 16 patients with a neurodevelopmental disorder characterized by delays, intellectual and learning disability, autism, behavioral abnormalities, and dysmorphic features. Most cases were de novo, with only one variant inherited from an affected parent. Here, we present seven additional individuals from five families with pathogenic or likely pathogenic JARID2 variants, confirming this gene-disease association and highlighting palatal abnormalities and heart defects as part of the phenotype. In addition, we report inheritance of JARID2 variants from mildly affected parents, demonstrating the variable expressivity of the disease. We also note the high prevalence of intragenic JARID2 copy number variants, emphasizing the importance of exon-level analysis.

La teoría de la mente (ToM) es un proceso cognitivo central de la cognición social, con gran importancia en la investigación en neurociencia y los trastornos neuropsiquiátricos. Un método usado para evaluar la ToM avanzada en adultos es la prueba de lectura de la mente a través de la mirada (RMET), que pese a ser ampliamente conocido en Perú aún carece de medidas estandarizadas y adecuadamente validadas para su aplicación en el área clínica y no clínica. Objetivos: 1. explorar las propiedades psicométricas del test de lectura de la mente a través de la mirada en los peruanos, así como el porcentaje de precisión para cada ítem entre las diferentes versiones del RMET; 2. obtener la fiabilidad test-retest tras un año de seguimiento. Se reclutaron 288 participantes de entre 17 y 55 años, de ambos sexos. Resultados: El RMET muestra una validez y consistencia media según la prueba KR-20, Alpha de Cronbach y Omega (0.645 – 0.666). Las mujeres tienen mejor rendimiento que hombres (p

Purpose To describe the clinical characteristics of children and adolescents that underwent diagnostic laparoscopy for suspected adnexal torsion (AT), and to develop a prediction model for preoperative detection of AT among young women. Methods A retrospective cohort study. We included all girls ≤18 years old with clinically suspected AT who underwent a diagnostic laparoscopy between 3/2011 and 6/2020. We compared patients with AT to those without AT and constructed a prediction model. Results Overall, 120 children and adolescents with suspected AT were included in the study. Of those, AT was identified in 83 (69.2%). In a multivariate analysis, the following risk factors were independently associated with AT and included in the prediction model: absence of right lower quadrant tenderness upon examination [adjusted odds ratio (aOR) (95% Confidence interval (CI)) 3.23 (1.23–8.47), p = 0.017], platelets level >240 K [aOR (95% CI) 3.15 (1.19–8.36), p = 0.021], and neutrophils level >5.4 [aOR (95% CI) 2.71 (1.02–7.52), p = 0.046]. The rate of AT was 12.5% in cases without risk factors for AT, 56.7% with one, 68.8% with two, and 94.1% with three risk factors present, respectively. Conclusions We have identified preoperative indicators independently associated with surgically confirmed AT in a large cohort of young women. Level of evidence- III

Summary Natural systems drive the high-energy reactions of photosynthesis with efficient and broadband energy capture. Transition-metal photocatalysts similarly convert light into chemical reactivity, and yet suffer from light-limited operation and require blue-to-UV excitation. In photosynthesis, both light capture and reactivity have been optimized by separation into distinct sites. Inspired by this modular architecture, we synthesized a biohybrid photocatalyst by covalent attachment of the photosynthetic light-harvesting protein R-phycoerythrin (RPE) to the transition-metal photocatalyst tris(2,2′-bipyridine)ruthenium(II) ([Ru(bpy)3]2+). Spectroscopic investigation found that absorbed photoenergy was efficiently funneled from RPE to [Ru(bpy)3]2+. The utility of the biohybrid photocatalyst was demonstrated via an increase in yields for a thiol-ene coupling reaction and a cysteinyl-desulfurization reaction, including recovered reactivity at red wavelengths where [Ru(bpy)3]2+ alone does not absorb.

Silk is a unique, remarkably strong biomaterial made of simple protein building blocks. To date, no synthetic method has come close to reproducing the properties of natural silk, due to the complexity and insufficient understanding of the mechanism of the silk fiber formation. Here, we use a combination of bulk analytical techniques and nanoscale analytical methods, including nano-infrared spectroscopy coupled with atomic force microscopy, to probe the structural characteristics directly, transitions, and evolution of the associated mechanical properties of silk protein species corresponding to the supramolecular phase states inside the silkworm’s silk gland. We found that the key step in silk-fiber production is the formation of nanoscale compartments that guide the structural transition of proteins from their native fold into crystalline β-sheets. Remarkably, this process is reversible. Such reversibility enables the remodeling of the final mechanical characteristics of silk materials. These results open a new route for tailoring silk processing for a wide range of new material formats by controlling the structural transitions and self-assembly of the silk protein’s supramolecular phases.

Hypomyelinating leukodystrophies comprise a subclass of genetic disorders with deficient myelination of the CNS white matter. Here we report four unrelated families with a hypomyelinating leukodystrophy phenotype harbouring variants in TMEM163 (NM_030923.5). The initial clinical presentation resembled Pelizaeus–Merzbacher disease with congenital nystagmus, hypotonia, delayed global development and neuroimaging findings suggestive of significant and diffuse hypomyelination. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. TMEM163 is highly expressed in the CNS particularly in newly myelinating oligodendrocytes and was recently revealed to function as a zinc efflux transporter. All the variants identified lie in highly conserved residues in the cytoplasmic domain of the protein, and functional in vitro analysis of the mutant protein demonstrated significant impairment in the ability to efflux zinc out of the cell. Expression of the mutant proteins in an oligodendroglial cell line resulted in substantially reduced mRNA expression of key myelin genes, reduced branching and increased cell death. Our findings indicate that variants in TMEM163 cause a hypomyelinating leukodystrophy and uncover a novel role for zinc homeostasis in oligodendrocyte development and myelin formation.

Transmembrane receptors are central components of the chemosensory systems by which motile bacteria detect and respond to chemical gradients. An attractant bound to the receptor periplasmic domain generates conformational signals that regulate a histidine kinase interacting with its cytoplasmic domain. Ligand-induced signaling through the periplasmic and transmembrane domains of the receptor involves a piston-like helical displacement, but the nature of this signaling through the >200 A four-helix coiled coil of the cytoplasmic domain had not yet been identified. We performed single-molecule Forster resonance energy transfer measurements on Escherichia coli aspartate receptor homodimers inserted into native phospholipid bilayers enclosed in nanodiscs. The receptors were labeled with fluorophores at diagnostic positions near the middle of the cytoplasmic coiled coil. At these positions, we found that the two N-helices of the homodimer were more distant, that is, less tightly packed and more dynamic than the companion C-helix pair, consistent with previous deductions that the C-helices form a stable scaffold and the N-helices are dynamic. Upon ligand binding, the scaffold pair compacted further, while separation and dynamics of the dynamic pair increased. Thus, ligand binding had asymmetric effects on the two helical pairs, shifting mean distances in opposite directions and increasing the dynamics of one pair. We suggest that this reflects a conformational change in which differential alterations to the packing and dynamics of the two helical pairs are coupled. These coupled changes could represent a previously unappreciated mode of conformational signaling that may well occur in other coiled-coil signaling proteins.

The burden of coronavirus disease 2019 (COVID-19) in children represents a fraction of cases worldwide, yet a subset of those infected are at risk for severe disease. We measured plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in a cohort of 103 children hospitalized with COVID-19 with diverse clinical manifestations. SARS-CoV-2 RNAemia was detected in 27 (26%) of these children, lasted for a median of 6 (interquartile range, 2–9) days, and was associated with higher rates of oxygen administration, admission to the intensive care unit, and longer hospitalization.

In the context of the global covid-19 pandemic, educators at all levels had to re-imagine their teaching practices to respond to the necessity of conducting all courses on-line. This article reports on the collaboration of two university instructors to create a trans-national model of learning in the context of the covid-19 pandemic. By virtue of this collaboration, the efl students based at a large public university in Colombia were engaged in four online sessions and paired with teacher candidates taking an esl endorsement course in the United States. This online collaboration afforded the Colombian efl students an authentic opportunity to practice their English learning and the us teacher candidates a meaningful context in which to conduct authentic language assessments. Using interview and questionnaire data, this qualitative case study explored the experiences of the efl students. The data demonstrate that online exchanges can afford students meaningful opportunities for language development. The results further show that online learning can be enriched through mutually beneficial collaborations across universities and transnational contexts. © 2021 Universidad de Antioquia. All Rights Reserved.

Carotenoids are accessory pigments in photosynthesis that serve a range of functions such as light harvesting, photoprotection, and structural stabilization. Such versatility is enabled by their unique electronic structure, which includes one or more dark excited states and is readily modulated by changes in their physical and chemical structures. In this review, we describe the ultrafast photophysical mechanisms of carotenoid-mediated energy transfer and energy dissipation, which underlie the light-harvesting and photoprotective functions of carotenoids in photosynthesis, and how recent developments in 2D electronic spectroscopy enable the investigation of these mechanisms. We focus on three light-harvesting complexes (LHCs) found in purple bacteria, green plants, and marine algae, which utilize distinct carotenoid molecules to optimize the photophysics for their survival and fitness.

A collisional-radiative (CR) model that extracts the electron temperature, T e, of hydrogen plasmas from Balmer-line-ratio measurements is examined for the plasma electron density, n e, and T e ranges of 1010–1015 cm−3 and 5–500 eV, respectively. The CR code, developed and implemented in Python, has a forward component that computes the densities of excited states up to n = 15 as functions of T e, n e, and the molecular-to-atomic neutral ratio r(H2/H). The backward component provides n e and r(H2/H) as functions of the Balmer ratios to predict the T e. The model assumes Maxwellian electrons. The density profiles of the electrons and of the molecular and atomic hydrogen neutrals are shown to be of great importance, as is the accuracy of the line-ratio measurement method.

A femtosecond two-photon-absorption laser-induced-fluorescence (TALIF) diagnostic was designed, installed, and operated on the Princeton-Field-Reversed Configuration-2 device to provide non-invasive measurements of the time and spatially resolved neutral-atom densities in its plasmas. Calibration of the H o density was accomplished by comparison with Kr TALIF. Measurements on plasmas formed of either H2 or Kr fill gases allowed examination of nominally long and short ionization mean-free-path regimes. With multi-kW plasma heating and H2 fill gas, a spatially uniform H o density of order 1017 m−3 was measured with better than ±2 mm and 10 µs resolution. Under similar plasma conditions but with Kr fill gas, a 3-fold decrease in the in-plasma Kr density was observed.

In green plants, light harvesting complex of Photosystem II (LHCII) absorbs and transports excitation energy toward the photosynthetic reaction centers and serves as a site for energy-dependent nonphotochemical quenching (qE), the photoprotective dissipation of energy as heat. LHCII is thought to activate dissipation through conformational changes that change the photophysical behaviors. Understanding this balance requires a characterization of how the conformations of LHCII, and thus its photophysics, are influenced by individual factors within the membrane environment. Here, we used ensemble and single-molecule fluorescence to characterize the excited-state lifetimes and switching kinetics of LHCII embedded in nanodisc- and liposome-based model membranes of various sizes and lipid compositions. As the membrane area decreased, the quenched population and the rate of conformational dynamics both increased because of interactions with other proteins, the aqueous solution, and/or disordered lipids. Although the conformational states and dynamics were similar in both thylakoid and asolectin lipids, photodegradation increased with thylakoid lipids, likely because of their charge and pressure properties. Collectively, these findings demonstrate the ability of membrane environments to tune the conformations and photophysics of LHCII.

Background Death at home has been identified as a key quality indicator for Canadian health care systems and is often assumed to reflect the wishes of the entire Canadian public. Although research in other countries has begun to question this assumption, there is a dearth of rigorous evidence of a national scope in Canada. This study addresses this gap and extends it by exploring three factors that moderate preferences for setting of death: situational severity (entailing both symptoms and supports), perceptions of family obligation, and respondent age. Methods Two thousand five hundred adult respondents from the general population were recruited using online panels between August 2019 and January 2020. The online survey included three vignettes, representing distinct dying scenarios which increased in severity based on symptom management alongside availability of formal and informal support. Following each vignette respondents rated their preference for each setting of death (home, acute/intensive care, palliative care unit, nursing home) for that scenario. They also provided sociodemographic information and completed a measure of beliefs about family obligations for end-of-life care. Results Home was the clearly preferred setting only for respondents in the mild severity scenario. As the dying scenario worsened, preferences fell for home death and increased for the other options, such that in the severe scenario, most respondents preferred a palliative care or hospice setting. This pattern was particularly distinct among respondents who also were less supportive of family obligation norms, and for adults 65 years of age and older. Conclusions Home is not universally the preferred setting for dying. The public, especially older persons and those expressing lower expectations of families in general, express greater preference for palliative care settings in situations where they might have less family or formal supports accompanied by more severe and uncontrolled symptoms. Findings suggest a) the need for public policy and health system quality indicators to reflect the nuances of public preferences, b) the need for adequate investment in hospices and palliative care settings, and c) continuing efforts to ensure that home-based formal services are available to help people manage symptoms and meet their preferences for setting of death.

Background Compassionate communities are rooted in a health promotion approach to palliative care, aiming to support solidarity among community members at the end of life. Hundreds of compassionate communities have been developed internationally in recent years. However, it remains unknown how their implementation on the ground aligns with core strategies of health promotion. The aim of this review is to describe the practical implementation and evaluation of compassionate communities. Methods We undertook a scoping review of the empirical peer-reviewed literature on compassionate communities. Bibliographic searches in five databases were developed with information specialists. We included studies in English describing health promotion activities applied to end-of-life and palliative care. Qualitative analysis used inductive and deductive strategies based on existing frameworks for categorization of health promotion activities, barriers and facilitators for implementation and evaluation measures. A participatory research approach with community partners was used to design the review and interpret its findings. Results Sixty-three articles were included for analysis. 74.6% were published after 2011. Health services organizations and providers are most often engaged as compassionate community leaders, with community members mainly engaged as target users. Adaptation to local culture and social context is the most frequently reported barrier for implementation, with support and external factors mostly reported as facilitators. Early stages of compassionate community development are rarely reported in the literature (stakeholder mobilization, needs assessment, priority-setting). Health promotion strategies tend to focus on the development of personal skills, mainly through the use of education and awareness programs. Few activities focused on strengthening community action and building healthy public policies. Evaluation was reported in 30% of articles, 88% of evaluation being analyzed at the individual level, as opposed to community processes and outcomes. Conclusions The empirical literature on compassionate communities demonstrates a wide variety of health promotion practices. Much international experience has been developed in education and awareness programs on death and dying. Health promotion strategies based on community strengthening and policies need to be consolidated. Future research should pay attention to community-led initiatives and evaluations that may not be currently reported in the peer-review literature.

OBJECTIVE To evaluate whether the adnexal twist degree is related to torsion recurrence and whether there is a dose-dependent correlation. DESIGN A retrospective cohort study. SETTING Single tertiary medical centre. POPULATION The study includes non-pregnant patients operated, for the first time, for adnexal torsion, between 2011 and 2018. METHODS Information regarding the degree of adnexal twist was collected from surgical reports. Recurrence was identified using a computerised database and ascertained via telephone with a response rate of 87.2% (253/290). MAIN OUTCOME MEASURES Adnexal torsion recurrence rate. RESULTS A total of 182 women who had undergone laparoscopic detorsion met the inclusion criteria. Twenty-two had torsion recurrence (12.1%). Adnexal twist degree in the primary event was associated with a higher recurrence risk: 4.3% of women with twist degree ≤360 (n = 3/70), 14.5% of women with twist degree of 361-720 (n = 9/62) and 20% of women with twist degree >720 (n = 10/50) (P = 0.03). The median twist degree was 540 (interquartile range [IQR] 360-855) and 720 (IQR 675-1080) degrees in the control and study groups, respectively (P = 0.005). Additional possibly associated factors for recurrence were evaluated. Age emerged as a possible risk factor, with a median age of 19 years in the recurrence group (IQR 14-27 years) versus 28.5 (IQR 19-36 years) in the non-recurrence group (P

The first JWST data on the massive colliding cluster El Gordo confirm 23 known families of multiply lensed images and identify 8 new members of these families. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and 9 were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range $20.8$ and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at $z=0.87$ and has an estimated mass of $3.8\times10^9$~\Msol, making it the smallest substructure found at $z>0.5$. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at $z=2.1878$. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at $z>6$, making more of them visible than in blank fields of similar size, but there appears to be a deficiency of such objects., Comment: 27 pages, 21 figures

The General Medical Council (GMC) plans to introduce a national Medical Licensing Assessment (MLA) in 2024 for all UK medical students as part of their primary medical qualification, with dermatology specified in its assessment blueprint. We present an Update to the British Association of Dermatologists' Undergraduate Curriculum, aligned both to the MLA Content Map and the GMC Outcomes for Graduates 2018.

Photocatalysis for organic synthesis is a tool capable of C–C, C–O and C–N bond transformations. This technology has the potential to transform the chemical manufacturing industry and support growing demand for chemical feedstocks. Compared to traditional catalysis, photocatalysis can access alternative reaction pathways that lower the overall energy requirement and operate at or near ambient conditions. A key challenge is the delivery of photoenergy at the scale required for rapid and efficient operation of the catalyst. The development of efficient, broad-spectrum light harvesting devices that funnel light energy to a catalyst, along with catalyst design to selectively enable high-energy reactions, are necessary steps towards solar fuels and feedstocks. This perspective highlights some recent advances in photocatalysis and advocates for expanding the scope of photocatalysis for large-scale industrial applications.

For more than a decade, photoredox catalysis has been demonstrating that when photoactive catalysts are irradiated with visible light, reactions occur under milder, cheaper, and environmentally friendlier conditions. Furthermore, this methodology allows for the activation of abundant chemicals into valuable products through novel mechanisms that are otherwise inaccessible. The photoredox approach, however, has been primarily used for pharmaceutical applications, where its implementation has been highly effective, but typically with a more rudimentary understanding of the mechanisms involved in these transformations. From a global perspective, the manufacture of everyday chemicals by the chemical industry as a whole currently accounts for 10% of total global energy consumption and generates 7% of the world's greenhouse gases annually. In this context, the Bio-Inspired Light-Escalated Chemistry (BioLEC) Energy Frontier Research Center (EFRC) was founded to supercharge the photoredox approach for applications in chemical manufacturing aimed at reducing its energy consumption and emissions burden, by using bioinspired schemes to harvest multiple electrons to drive endothermically uphill chemical reactions. The Center comprises a diverse group of researchers with expertise that includes synthetic chemistry, biophysics, physical chemistry, and engineering. The team works together to gain a deeper understanding of the mechanistic details of photoredox reactions while amplifying the applications of these light-driven methodologies.In this Account, we review some of the major advances in understanding, approach, and applicability made possible by this collaborative Center. Combining sophisticated spectroscopic tools and photophysics tactics with enhanced photoredox reactions has led to the development of novel techniques and reactivities that greatly expand the field and its capabilities. The Account is intended to highlight how the interplay between disciplines can have a major impact and facilitate the advance of the field. For example, techniques such as time-resolved dielectric loss (TRDL) and pulse radiolysis are providing mechanistic insights not previously available. Hypothesis-driven photocatalyst design thus led to broadening of the scope of several existing transformations. Moreover, bioconjugation approaches and the implementation of triplet-triplet annihilation mechanisms created new avenues for the exploration of reactivities. Lastly, our multidisciplinary approach to tackling real-world problems has inspired the development of efficient methods for the depolymerization of lignin and artificial polymers.

Qualitative accounts indicate there are sensory and communication related barriers to adequate childbirth and postnatal healthcare for autistic people. However, little quantitative work has explored the topic. This online survey study explored childbirth and postnatal experiences among 384 autistic and 492 non-autistic people. Compared with non-autistic people, autistic people were more likely to find the sensory aspects of birth overwhelming, and experienced lower satisfaction with birth-related and postnatal healthcare. Autistic people were more likely to experience postnatal depression and anxiety. The findings highlight that sensory and communication adjustments should be made to birth and postnatal healthcare for autistic people. The findings indicate the need for greater autism understanding among professionals and greater postnatal mental health support for autistic people.