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Channelrhodopsins are light-sensitive ion channels whose reaction cycles involve conformation-coupled transfer of protons. Understanding how channelrhodopsins work is important for applications in optogenetics, where light activation of these proteins triggers changes in the transmembrane potential across excitable membranes. A fundamental open question is how the protein environment ensures that unproductive proton transfer from the retinal Schiff base to the nearby carboxylate counterion is avoided in the resting state of the channel. To address this question, we performed combined quantum mechanical/molecular mechanical proton transfer calculations with explicit treatment of the surrounding lipid membrane. The free energy profiles computed for proton transfer to the counterion, either via a direct jump or mediated by a water molecule, demonstrate that, when retinal is all-trans, water and protein electrostatic interactions largely favour the protonated retinal Schiff base state. We identified a conserved lysine group as an essential structural element for the proton transfer energetics in channelrhodopsins.

Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs. Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.

The Rhizoclosmatium globosum genome encodes three rhodopsin-guanylyl cyclases (RGCs), which are predicted to facilitate visual orientation of the fungal zoospores. Here, we show that RGC1 and RGC2 function as light-activated cyclases only upon heterodimerization with RGC3 (NeoR). RGC1/2 utilize conventional green or blue-light-sensitive rhodopsins ( λ max  = 550 and 480 nm, respectively), with short-lived signaling states, responsible for light-activation of the enzyme. The bistable NeoR is photoswitchable between a near-infrared-sensitive (NIR, λ max  = 690 nm) highly fluorescent state ( Q F  = 0.2) and a UV-sensitive non-fluorescent state, thereby modulating the activity by NIR pre-illumination. No other rhodopsin has been reported so far to be functional as a heterooligomer, or as having such a long wavelength absorption or high fluorescence yield. Site-specific mutagenesis and hybrid quantum mechanics/molecular mechanics simulations support the idea that the unusual photochemical properties result from the rigidity of the retinal chromophore and a unique counterion triad composed of two glutamic and one aspartic acids. These findings substantially expand our understanding of the natural potential and limitations of spectral tuning in rhodopsin photoreceptors. Rhizoclosmatium globosum contains three rhodopsin-guanylyl cyclases (RGCs) predicted to enable visual orientation of zoospores. Here authors show that RGC1 and 2 function as light-activated cyclases only upon heterodimerization with RGC3 (NeoR), a near-infrared absorbing, highly fluorescent rhodopsin.

The biological function of phytochromes is triggered by an ultrafast photoisomerization of the tetrapyrrole chromophore biliverdin between two rings denoted C and D . The mechanism by which this process induces extended structural changes of the protein is unclear. Here we report ultrafast proton-coupled photoisomerization upon excitation of the parent state (Pfr) of bacteriophytochrome Agp2. Transient deprotonation of the chromophore’s pyrrole ring D or ring C into a hydrogen-bonded water cluster, revealed by a broad continuum infrared band, is triggered by electronic excitation, coherent oscillations and the sudden electric-field change in the excited state. Subsequently, a dominant fraction of the excited population relaxes back to the Pfr state, while ~35% follows the forward reaction to the photoproduct. A combination of quantum mechanics/molecular mechanics calculations and ultrafast visible and infrared spectroscopies demonstrates how proton-coupled dynamics in the excited state of Pfr leads to a restructured hydrogen-bond environment of early Lumi-F, which is interpreted as a trigger for downstream protein structural changes. Phytochromes regulate plant growth by sensing far-red light through the photoisomerization of their protein-bound chromophores. In the phytochrome Agp2, it has now been demonstrated that ultrafast proton-transfer occurs from the chromophore to a protein–water network before photoisomerization, inducing protein changes on the ultrafast timescale. These protein changes develop further on longer timescales, resulting in an activated protein conformation.

Many organisms sense light using rhodopsins, photoreceptive proteins containing a retinal chromophore. Here we report the discovery, structure and biophysical characterization of bestrhodopsins, a microbial rhodopsin subfamily from marine unicellular algae, in which one rhodopsin domain of eight transmembrane helices or, more often, two such domains in tandem, are C-terminally fused to a bestrophin channel. Cryo-EM analysis of a rhodopsin-rhodopsin-bestrophin fusion revealed that it forms a pentameric megacomplex (~700 kDa) with five rhodopsin pseudodimers surrounding the channel in the center. Bestrhodopsins are metastable and undergo photoconversion between red- and green-absorbing or green- and UVA-absorbing forms in the different variants. The retinal chromophore, in a unique binding pocket, photoisomerizes from all- trans to 11- cis form. Heterologously expressed bestrhodopsin behaves as a light-modulated anion channel. Functional and structural characterization of rhodopsin-bestrophin fusion proteins from marine algae unveils the existence of giant light-sensitive anion channels with unusual biophysical properties.

Channelrhodopsins (ChR) are light-gated ion-channels heavily used in optogenetics. Upon light excitation an ultrafast all-trans to 13-cis isomerization of the retinal chromophore takes place. It is still uncertain by what means this reaction leads to further protein changes and channel conductivity. Channelrhodopsin-1 in Chlamydomonas augustae exhibits a 100 fs photoisomerization and a protonated counterion complex. By polarization resolved ultrafast spectroscopy in the mid-IR we show that the initial reaction of the retinal is accompanied by changes in the protein backbone and ultrafast protonation changes at the counterion complex comprising Asp299 and Glu169. In combination with homology modelling and quantum mechanics/molecular mechanics (QM/MM) geometry optimization we assign the protonation dynamics to ultrafast deprotonation of Glu169, and transient protonation of the Glu169 backbone, followed by a proton transfer from the backbone to the carboxylate group of Asp299 on a timescale of tens of picoseconds. The second proton transfer is not related to retinal dynamics and reflects pure protein changes in the first photoproduct. We assume these protein dynamics to be the first steps in a cascade of protein-wide changes resulting in channel conductivity.

Background: The occurrence of challenges associated with the health of the aged keeps increasing due to the increasing aged population. One of the most common among these is depression. Depression is a prevalent mental illness that is defined by prolonged melancholy, loss of interest in once-enjoyed pursuits, and the inability to carry out everyday tasks for at least two weeks. The study analyzed the contributing factors associated with depression among the ageing population of Ghana. Method: The study used the World Health Organization’s Study on global AGEing and adult health (SAGE) wave 1 data from Ghana. There were 4,223 participants in the data. Descriptive statistics and logistic regression were used for data analysis. A logistic regression model was developed using the data. Results: The findings indicated that 52.76% of the elderly suffered depression. The prevalence of depression is higher among older adults with severe or moderate vision issues. Additionally, it was shown that those with medium levels of education experience depression more frequently than those with no education or low levels of education. Again, older people with memory problems are more prone to depression. The logistic regression found difficulty in seeing, highest education level, systolic blood pressure, alcohol intake, and difficulty in remembering as the risk factors associated with depression. Conclusions: The prevalence of depression among the aged in Ghana is high. Since depressive symptoms are frequently linked to aging, we advise health practitioners to screen depressive symptoms alongside other chronic medical conditions in the elderly population in healthcare facilities and community settings.

Maternal hyperuricemia is a potential biomarker of adverse pregnancy outcomes, but evidence among normotensive women in low- and middle-income countries is limited. We aimed to assess the association between elevated maternal serum uric acid (SUA) levels and adverse neonatal outcomes. We conducted a prospective cohort study at Jinja Regional Referral Hospital, Uganda, from 1st October 2024-1st February 2025, enrolling 352 normotensive women in latent labor. SUA was measured using gestational-age-specific cutoffs, classifying women as hyperuricemic or normouricemic. Outcomes included preterm birth, small-for-gestational-age (SGA) birth, stillbirth, and low Apgar score. Poisson regression with robust standard errors estimated adjusted relative risks (aRR) and 95% confidence intervals. Adverse neonatal outcomes occurred in 37.5% of participants. Hyperuricemic women had significantly higher composite risk (62.5% vs. 12.5%; aRR = 4.32, 95% CI 2.92-6.39). Hyperuricemia independently predicted preterm birth (aRR = 3.63, 95% CI 1.70-7.72), SGA (aRR = 2.80, 95% CI 1.61-4.86), and stillbirth (aRR = 5.00, 95% CI 1.47-16.99). Maternal age ≥ 40 years, low education, < 4 antenatal visits, previous preterm birth, previous stillbirth, and obesity were also associated with adverse outcomes. Conclusions. Maternal hyperuricemia is a strong predictor of preterm birth, SGA, and stillbirth. Routine SUA screening during antenatal care, combined with closer monitoring of high-risk women, could help improve neonatal outcomes.

Background and Aims Vitamin D deficiency in pregnancy has been linked to adverse maternal and neonatal outcomes, but evidence from Uganda is limited. We estimated the prevalence of maternal vitamin D deficiency at delivery, identified associated factors, and assessed immediate neonatal outcomes. Methods We conducted a hospital‐based cross‐sectional study among 315 postpartum women at Jinja Regional Referral Hospital (October 2024–January 2025). Serum 25‐hydroxyvitamin D was measured; deficiency was defined as < 20 ng/mL. Predictors were assessed using logistic regression. Neonatal outcomes were extracted from delivery records. Results Vitamin D deficiency was present in 77.8% (245/315) of participants; mean 25(OH)D was 18.3 (SD 7.5) ng/mL. Urban residence, low educational attainment, higher BMI, fewer antenatal visits, and lack of regular exercise were independently associated with deficiency. Low 5‐min Apgar score was more frequent among neonates of deficient mothers. Conclusions Maternal vitamin D deficiency was highly prevalent and associated with modifiable factors. Maternal deficiency was associated with poorer immediate neonatal indicators at birth; however, neonatal vitamin D levels were not measured and causality cannot be inferred.