Differences in the Interleukin Profiles in Inattentive ADHD Prepubertal Children Are Probably Related to Conduct Disorder Comorbidity.

Inflammatory cytokines are involved in attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder. To quantify the baseline levels of pro- and anti-inflammatory cytokines and their changes after methylphenidate (MPH), a total of 31 prepubertal children with ADHD were recruited and subclassified into only two ADHD presentations-ADHD attention deficit (n = 13) or ADHD combined (n = 18). The children were also screened for oppositional defiant conduct disorder (ODCD) and anxiety disorder. Blood samples were drawn at 09:00 and after 4.63 ± 1.87 months of treatment. Four pro-inflammatory cytokines (interleukin-1beta (IL-1ß), IL-5, IL-6, tumor necrosis factor-alpha (TNF-α)) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were measured using a Luminex® assay. For statistics, a factorial analysis was performed in Stata 15.1. Overall, there were no statistically significant differences in the interleukin (IL) values induced by treatment. When grouped by presentation, the differences were present almost exclusively in ADHD-AD, usually with a profile opposite to that observed in ADHD-C, and with interactions between comorbid factors, with IL-1ß (p = 0.01) and IL-13 (p = 0.006) being the ones reaching the greatest statistical significance. These differences are probably related to the ODCD factor, and they disappear after treatment. In conclusion, the changes observed in cytokine levels in prepubertal children only in the ADHD-AD presentation are probably related to comorbidities (specifically ODCD) and are mitigated after treatment.

Tracking the brain signature of (mis)spelled logotypes via letter transpositions and replacements.

All leading models of visual word recognition assume a hierarchical process that progressively converts the visual input into abstract letter and word representations. However, the results from recent behavioral studies suggest that the mental representations of words with a highly consistent visual format, such as logotypes, may comprise not only purely abstract information but also perceptual information. This hypothesis would explain why participants often misperceive transposed-letter misspellings with the original base words to a larger degree in logotypes (e.g., SASMUNG, but not SARVUNG, is perceived as SAMSUNG) than in common words. The present experiment examined the electrophysiological signature behind the identification of correctly spelled and misspelled logotypes (via letter transposition or replacement) in an ERP go/no-go semantic categorization experiment. Results showed that N400 amplitudes for transposed-letter misspelled logotypes (SASMUNG) and intact logotypes (SAMSUNG) did not differ significantly across various time windows (until 600 ms), whereas replacement-letter misspelled logotypes (SARVUNG) yielded consistently larger N400 amplitudes. These findings reveal that the mental representations of logotypes are particularly resistant to minor orthographic changes, which has important theoretical and applied (e.g., marketing) implications.

Changes in Cortisol and in Oxidative/Nitrosative Stress Indicators after ADHD Treatment.

Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, as well as the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results showed a treatment-related improvement in the redox profile, with the reduction in advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase in the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These results support, for the first time, the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

One more trip to Barcetona: on the special status of visual similarity effects in city names.

Previous research has shown that, unlike misspelled common words, misspelled brand names are sensitive to visual letter similarity effects (e.g., amazom is often recognized as a legitimate brand name, but not amazot). This pattern poses problems for those models that assume that word identification is exclusively based on abstract codes. Here, we investigated the role of visual letter similarity using another type of word often presented in a more homogenous format than common words: city names. We found a visual letter similarity effect for misspelled city names (e.g., Barcetona was often recognized as a word, but not Barcesona) for relatively short durations of the stimuli (200 ms; Experiment 2), but not when the stimuli were presented until response (Experiment 1). Notably, misspelled common words did not show a visual letter similarity effect for brief 200- and 150-ms durations (e.g., votume was not as often recognized as a word than vosume; Experiments 3-4). These findings provide further evidence that the consistency in the format of presentations may shape the representation of words in the mental lexicon, which may be more salient in scenarios where processing resources are limited (e.g., brief exposure presentations).

Examining Letter Detector Tolerance through Offset Letter Halves: Evidence from Lexical Decision.

Neurobiological models of reading assume that the specialized detectors at the letter level (e.g., the arrays of detectors for the letter 'n') possess a certain degree of tolerance (e.g., Local Combination Detectors model, Dehaene et al. 2005). In this study, we designed two lexical decision experiments that examined the limits of tolerance of letter detectors by introducing a novel manipulation involving shifting letter halves (e.g., in Experiment 1; in Experiment 2) relative to intact items. This manipulation alters the transition between upper and lower parts of the letters, adding junctions that do not exist in the intact letter forms. We included high- and low-frequency words in the stimulus list to investigate whether letter distortion affects processing beyond the letter level, reasoning that interactive effects would signal top-down lexical feedback. In Experiment 1, which employed a subtle letter shift, we observed a minimal cost of letter distortion that did not interact with word frequency. Experiment 2, employing a larger letter shift, revealed an overall greater reading cost that affected differentially high- and low-frequency words. Overall, these findings offer insights into the limits of resilience in letter detectors to distortion during word recognition and introduce a novel manipulation of letter distortion.

Breaking the boundaries: the power of ligatures in visual-word recognition.

Introduction: Current neurobiological-inspired models of visual-word recognition propose that letter detectors in the word recognition system can tolerate some variations in the visual form of the letters. However, it is unclear whether this tolerance extends to novel ligatures, which combine two letters into a single glyph. Methods: To investigate this, the present study utilized a masked priming experiment with a lexical decision task to examine whether primes containing novel ligatures are effective in activating their corresponding base word, relative to omitted-letter primes, in the initial stages of word processing. For each target word (e.g., VIRTUAL), were created an identity prime (virtual), a prime containing a novel ligature of two of the letters (e.g., virtual; "ir" in a single glyph), and an omitted-letter prime where one letter was removed (e.g., vrtual [omitted-vowel] in Experiment 1; vitual [omitted-consonant] in Experiment 2). Results: Results showed that the presence of a novel ligature in the prime resulted in faster lexical decision times compared to a prime with an omitted vowel (Experiment 1), but not with an omitted consonant (Experiment 2). Furthermore, the performance with the primes containing the novel ligature was not different from that of the identity primes. Discussion: These results suggest that the word recognition system can quickly enable separate letter detectors for novel ligatures. These findings have important implications for our understanding of the front-end of visual-word recognition.

A Letter is a Letter and its Co-Occurrences: Cracking the Emergence of Position-Invariance Processing.

Visual word recognition requires encoding letter identities and positions (orthographic processing). The present study focuses on the emergence of the mechanism responsible for encoding letter order in a word: position invariance. Reading experience leads to developing a flexible mechanism that encodes the information of the position of letters, explaining why jugde and judge are easily confused. Critically, orthographic regularities (e.g., frequent letter co-occurrences) modulate letter position encoding: the pseudoword mohter is extremely similar to mother because, in middle positions, the bigram TH is much more frequent than HT. Here, we tested whether position invariance emerges rapidly after the exposition to orthographic regularities-bigrams-in a novel script. To that end, we designed a study with two phases. In Phase 1, following Chetail (2017; Experiment 1b, Cognition, 163, 103-120), individuals were first exposed to a flow of artificial words for a few minutes, with four bigrams occurring frequently. Afterward, participants judged the strings with trained bigrams as more wordlike (i.e., readers quickly picked up subtle new orthographic regularities) than the strings with untrained bigrams, replicating Chetail (2017). In Phase 2, participants performed a same-different matching task in which they had to decide whether pairs of five-letter strings were the same or not. The critical comparison was between pairs with a transposition of letters in a frequent (trained) versus infrequent (untrained) bigram. Results showed that participants were more prone to make errors with frequent bigrams than with infrequent bigrams with a letter transposition. These findings reveal that position invariance emerges rapidly, after continuous exposure to orthographic regularities.

Investigating the Role of Response Codes in Masked Priming Lexical Decision Tasks: The Case of Repeated Presentations.

The masked priming technique is considered a gold standard among experimental psychologists who specialize in the field of visual word recognition. Typically, this method entails a comparison between two or more critical conditions (e.g., the target word MOUSE being preceded by either the identity prime mouse or the unrelated prime fence). It is noteworthy that, unlike other masked priming tasks, prior experiments examining the properties of unrelated primes (e.g., their frequency as words [high or low] or their legality as nonwords [orthographically legal or illegal]) do not have an impact on the processing of the target item. However, two lexical decision studies reported faster responses to target words when the unrelated prime is a word rather than a nonword (i.e., a response congruency effect). One possible explanation for this discrepancy is a difference in methodology, as these two studies are the only ones to have used repeated presentation of stimuli, which could lead to the creation of an episodic memory trace that amplifies response congruency effects. To examine this hypothesis, we used a set of materials that did not show any congruency effect in a previous experiment with unique presentations, except that here we included repeated presentations. Results showed a response congruency effect, with participants responding faster to word targets when they were preceded by an unrelated word prime as opposed to an unrelated nonword prime. These findings suggest that the activation of response codes in masked priming is contingent upon the nature of cognitive resources required for processing the target stimuli.

Perceptual Contiguity Does Not Modulate Matched-Case Identity-Priming Effects in Lexical Decision.

In recent studies with the masked priming lexical decision task, matched-case identity-priming effects occur for nonwords but not for words (e.g., nonwords: ERTAR-ERTAR faster than ertar-ERTAR; words: ALTAR-ALTAR produces similar response times as altar-ALTAR). This dissociation is thought to result from lexical feedback influencing orthographic representations in word processing. As nonwords do not receive this feedback, bottom-up processing of prime-target integration leads to matched-case effects. However, the underlying mechanism of this effect in nonwords remains unclear. In this study, we added a color congruency manipulation across the prime and target in the matched-case identity-priming design. We aimed to determine whether the case effects originate at the early stages of prime-target perceptual integration or due to bottom-up activation of case-specific letter detectors. Results replicated the previous dissociation between words and nonwords regarding the matched-case identity effect. Additionally, we did not find any modulation of these effects by prime-target color congruency. These findings suggest that the locus of the matched-case identity effect is at an orthographic level of representation that encodes case information.

[Immunonutrition, evidence and experiences]. / Inmunonutrición, evidencias y experiencias.

Introduction: Immunonutrition is a science that encompasses aspects related to nutrition, immunity, infection, inflammation and tissue damage. Immunomodulatory formulas have shown benefits in a wide variety of clinical situations. The objective of this work was to review the available evidence in immunonutrition (IN). For this, a bibliographic search has been carried out with the keywords: immunonutrition, arginine, glutamine, nucleotides, omega-3 fatty acids, ERAS, fast-track. Clinical trials, reviews and clinical practice guidelines have been included. IN has been shown to reduce postoperative fistulae in head and neck cancer patients and in gastric and esophageal cancer patients, infectious complications and hospital stay. Other clinical situations that benefit from the use of IN are pancreatic cancer surgery, colorectal cancer surgery and major burns. More controlled, prospective, and randomized studies are necessary to confirm the potential benefits of IN in other clinical situations such as non-esophageal thoracic surgery, bladder cancer, gynecological surgery, hip fracture, liver pathology and COVID-19, among others.

Introducción: La inmunonutrición es una ciencia que engloba aspectos relacionados con la nutrición, la inmunidad, la infección, la inflamación y el daño tisular. Las fórmulas inmunomoduladoras han demostrado beneficios en una amplia variedad de situaciones clínicas. El objetivo de este trabajo es revisar la evidencia disponible en inmunonutrición (IN). Para ello, se ha realizado una búsqueda bibliográfica con las palabras clave: inmunonutrición, arginina, glutamina, nucleótidos, ácidos grasos omega-3, ERAS, fast-track. Se han incluido ensayos clínicos, revisiones y guías de práctica clínica. La IN ha demostrado reducir las fístulas en el postoperatorio en pacientes con cáncer de cabeza y cuello. En pacientes con cáncer gástrico y cáncer de esófago, la IN se asocia a una disminución de las complicaciones infecciosas y la estancia hospitalaria. Otras situaciones clínicas que se benefician del uso de la IN son la cirugía del cáncer de páncreas, la cirugía del cáncer colorrectal y los grandes quemados. Son necesarios más estudios controlados, prospectivos y aleatorizados para confirmar los potenciales beneficios de la IN en otras situaciones clínicas como la cirugía torácica no esofágica, el cáncer vesical, la cirugía ginecológica, la fractura de cadera, la patología hepática y la COVID-19, entre otros.

On the time course of the tolerance of letter detectors to rotations: A masked priming ERP investigation.

A straightforward prediction of the Local Combination Detectors [LCD] model of word recognition (Dehaene et al., 2005) is that letter rotations above 40-45° should disrupt the mapping of the visual input onto orthographic representations. However, the evidence supporting this claim is scarce and not conclusive. To shed light on this issue, we conducted a masked repetition priming lexical decision experiment while recording the participants' EEG measures. Targets were always presented in the standard horizontal format, and we rotated the individual letters of the identity/unrelated primes (0°, 45°, or 90°). Behavioral and Event-Related Potentials (ERP) results revealed that the identity priming effect decreased as a function of letter rotation. Importantly, the ERP data allowed us to examine in detail the time course of processing of words with rotated letters. Amplitude comparisons showed that identity priming followed the typical course for 0° primes (i.e., it started around 100 ms, in the visual feature encoding stage, and strengthened with processing time). The parallel effect for 45° primes emerged later, at around 175 ms. This pattern strongly suggests that letter rotations at around 45° have a processing cost, thus providing evidence in favor of the LCD model of word recognition (Dehaene et al., 2005).

Are brand names special words? Letter visual-similarity affects the identification of brand names, but not common words.

Brand names are often considered a special type of words of special relevance to examine the role of visual codes during reading: unlike common words, brand names are typically presented with the same letter-case configuration (e.g., IKEA, adidas). Recently, Pathak et al. (European Journal of Marketing, 2019, 53, 2109) found an effect of visual similarity for misspelled brand names when the participants had to decide whether the brand name was spelled correctly or not (e.g., tacebook [baseword: facebook] was responded more slowly and less accurately than xacebook). This finding is at odds with both orthographically based visual-word recognition models and prior experiments using misspelled common words (e.g., viotin [baseword: violin] is identified as fast as viocin). To solve this puzzle, we designed two experiments in which the participants had to decide whether the presented item was written correctly. In Experiment 1, following a procedure similar to Pathak et al. (European Journal of Marketing, 2019, 53, 2109), we examined the effect of visual similarity on misspelled brand names with/without graphical information (e.g., anazon vs. atazon [baseword: amazon]). Experiment 2 was parallel to Experiment 1, but we focused on misspelled common words (e.g., anarillo vs. atarillo; baseword: amarillo [yellow in Spanish]). Results showed a sizeable effect of visual similarity on misspelled brand names - regardless of their graphical information, but not on misspelled common words. These findings suggest that visual codes play a greater role when identifying brand names than common words. We examined how models of visual-word recognition can account for this dissociation.

[Benefits of a community physical exercise program prescribed from primary care for perimenopausal/menopausal women]. / Beneficios de un programa de ejercicio físico comunitario prescrito desde Atención Primaria en la salud de mujeres perimenopáusicas/menopaúsicas.

OBJECTIVE: To measure the benefits of a physical exercise program in a community, through the modifications in quality of life, and perimenopausal-menopausal women physical condition. SETTING: The participants were recruited in PC consultations from two health centers in Molina de Segura (Murcia). PARTICIPANTS: Women between 40 and 70 years old, or under 40 of age diagnosed with early menopause. DESIGN: Quasi-experimental study, non-randomized, controlled, open and single-center with 2 parallel branches to study. INTERVENTION: Experimental group: ACTIVA Bone Health Program for six months. CONTROL: inactive. MAIN MEASUREMENTS IN BOTH GROUPS: The SF 36 questionnaire was used to measure the Quality of life. PHYSICAL CONDITION: Aerobic condition, flexibility, balance and strength measured with the mile, flamenco, flexibility box tests, and throwing the medicine ball, respectively. Physical activity level through the GPPAQ Questionnaire. Sociodemographic variables were collected and the adherence to the program was measured. RESULTS: The quality of life improved in the intervention group compared to the control group, except «Body Pain¼ dimension (p = 0.412). As regards the intragroup level, all dimensions showed significant improvement except both «Physical Function¼ (p = 0.263) and «Body Pain¼ (p = 0.136). The physical capacities that benefited most were aerobic fitness, strength and balance. CONCLUSIONS: The Active Bone Health Physical Exercise Program piloting showed benefits on participants' physical and mental quality of life. In addition, it has been shown that performing a specific physical exercise for premenopausal-menopausal women improves their physical condition.

Unveiling the boost in the sandwich priming technique.

The masked priming technique (which compares #####-house-HOUSE vs. #####-fight-HOUSE) is the gold-standard tool to examine the initial moments of word processing. Lupker and Davis showed that adding a pre-prime identical to the target produced greater priming effects in the sandwich technique (which compares #####-HOUSE-house-HOUSE vs #####-HOUSE-fight-HOUSE). While there is consensus that the sandwich technique magnifies the size of priming effects relative to the standard procedure, the mechanisms underlying this boost are not well understood (i.e., does it reflect quantitative or qualitative changes?). To fully characterise the sandwich technique, we compared the sandwich and standard techniques by examining the response times (RTs) and their distributional features (delta plots; conditional-accuracy functions), comparing identity versus unrelated primes. The results showed that the locus of the boost in the sandwich technique was two-fold: faster responses in the identity condition (via a shift in the RT distributions) and slower responses in the unrelated condition. We discuss the theoretical and methodological implications of these findings.

The Omission of Accent Marks Does Not Hinder Word Recognition: Evidence From Spanish.

Recent research has found that the omission of accent marks in Spanish does not produce slower word identification times in go/no-go lexical decision and semantic categorization tasks [e.g., cárcel (prison) = carcel], thus suggesting that vowels like á and a are represented by the same orthographic units during word recognition and reading. However, there is a discrepant finding with the yes/no lexical decision task, where the words with the omitted accent mark produced longer response times than the words with the accent mark. In Experiment 1, we examined this discrepant finding by running a yes/no lexical decision experiment comparing the effects for words and non-words. Results showed slower response times for the words with omitted accent mark than for those with the accent mark present (e.g., cárcel < carcel). Critically, we found the opposite pattern for non-words: response times were longer for the non-words with accent marks (e.g., cárdil > cardil), thus suggesting a bias toward a "word" response for accented items in the yes/no lexical decision task. To test this interpretation, Experiment 2 used the same stimuli with a blocked design (i.e., accent mark present vs. omitted in all items) and a go/no-go lexical decision task (i.e., respond only to "words"). Results showed similar response times to words regardless of whether the accent mark was omitted (e.g., cárcel = carcel). This pattern strongly suggests that the longer response times to words with an omitted accent mark in yes/no lexical decision experiments are a task-dependent effect rather than a genuine reading cost.

Which Factors Modulate Letter Position Coding in Pre-literate Children?

One of the central landmarks of learning to read is the emergence of orthographic processing (i.e., the encoding of letter identity and letter order): it constitutes the necessary link between the low-level stages of visual processing and the higher-level processing of words. Regarding the processing of letter position, many experiments have shown worse performance in various tasks for the transposed-letter pair judge-JUDGE than for the orthographic control jupte-JUDGE. Importantly, 4-y.o. pre-literate children also show letter transposition effects in a same-different task: TZ-ZT is more error-prone than TZ-PH. Here, we examined whether this effect with pre-literate children is related to the cognitive and linguistic skills required to learn to read. Specifically, we examined the relation of the transposed-letter in a same-different task with the scores of these children in phonological, alphabetic and metalinguistic awareness, linguistic skills, and basic cognitive processes. To that end, we used a standardized battery to assess the abilities related with early reading acquisition. Results showed that the size of the transposed-letter effect in pre-literate children was strongly associated with the sub-test on basic cognitive processes (i.e., memory and perception) but not with the other sub-tests. Importantly, identifying children who may need a pre-literacy intervention is crucial to minimize eventual reading difficulties. We discuss how this marker can be used as a tool to anticipate reading difficulties in beginning readers.

How resilient is reading to letter rotations? A parafoveal preview investigation.

Skilled readers have developed a certain amount of tolerance to variations in the visual form of words (e.g., CAPTCHAs, handwritten text, etc.). To examine how visual distortion affects the mapping from the visual input onto abstract word representations during normal reading, we focused on a single type of distortion: letter rotation. Importantly, two leading neurally inspired models of word recognition (SERIOL model, Whitney, 2001; LCD model, Dehaene et al., 2005) make distinct predictions: Whereas the SERIOL model postulates that the cost of letter rotation increases gradually, the LCD model assumes an all-or-none boundary at around 40° to 45° rotation angle. To examine these predictions in a normal reading scenario, we conducted a parafoveal preview experiment using the gaze-contingent boundary change paradigm. The parafoveal previews were identical or unrelated to the target word. Critically, each preview's individual letters were rotated 15°, 30°, 45°, or 60°. Apart from the parafoveal previews, all text, including target words, was presented with letters in their canonical upright orientation. Results showed that the advantage of the identity preview condition in eye fixation times on the target word decreased progressively by rotation angle. This pattern of results favors the view that the cost of letter rotation during normal reading increases gradually as a function of the angle of rotation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Do Grading Gray Stimuli Help to Encode Letter Position?

Numerous experiments in the past decades recurrently showed that a transposed-letter pseudoword (e.g., JUGDE) is much more wordlike than a replacement-letter control (e.g., JUPTE). Critically, there is an ongoing debate as to whether this effect arises at a perceptual level (e.g., perceptual uncertainty at assigning letter position of an array of visual objects) or at an abstract language-specific level (e.g., via a level of "open bigrams" between the letter and word levels). Here, we designed an experiment to test the limits of perceptual accounts of letter position coding. The stimuli in a lexical decision task were presented either with a homogeneous letter intensity or with a graded gray intensity, which indicated an unambiguous letter order. The pseudowords were either transposed-letter pseudowords or replaced-letter pseudowords (e.g., jugde vs. jupte). The results showed much longer response times and substantially more errors in the transposed-letter pseudowords than in the replacement-letter pseudowords, regardless of visual format. These findings favor the idea that language-specific orthographic element factors play an essential role when encoding letter position during word recognition.

Does orthographic processing emerge rapidly after learning a new script?

Orthographic processing is characterized by location-invariant and location-specific processing (Grainger, 2018): (1) strings of letters are more vulnerable to transposition effects than the strings of symbols in same-different tasks (location-invariant processing); and (2) strings of letters, but not strings of symbols, show an initial position advantage in target-in-string identification tasks (location-specific processing). To examine the emergence of these two markers of orthographic processing, we conducted a same-different task and a target-in-string identification task with two unfamiliar scripts (pre-training experiments). Across six training sessions, participants learned to fluently read and write one of these scripts. The post-training experiments were parallel to the pre-training experiments. Results showed that the magnitude of the transposed-letter effect in the same-different task and the serial function in the target-in-string identification tasks were remarkably similar for the trained and untrained scripts. Thus, location-invariant and location-specific processing does not emerge rapidly after learning a new script; instead, they may require thorough experience with specific orthographic structures.

Intramolecular Proton Transfer Controls Protein Structural Changes in Phytochrome.

Phytochromes are biological photoswitches that interconvert between two parent states (Pr and Pfr). The transformation is initiated by photoisomerization of the tetrapyrrole chromophore, followed by a sequence of chromophore and protein structural changes. In the last step, a phytochrome-specific peptide segment (tongue) undergoes a secondary structure change, which in prokaryotic phytochromes is associated with the (de)activation of the output module. The focus of this work is the Pfr-to-Pr photoconversion of the bathy bacteriophytochrome Agp2 in which Pfr is the thermodynamically stable state. Using spectroscopic techniques, we studied the structural and functional consequences of substituting Arg211, Tyr165, His278, and Phe192 close to the biliverdin (BV) chromophore. In Pfr, substitutions of these residues do not affect the BV structure. The characteristic Pfr properties of bathy phytochromes, including the protonated propionic side chain of ring C (propC) of BV, are preserved. However, replacing Arg211 or Tyr165 blocks the photoconversion in the Meta-F state, prior to the secondary structure transition of the tongue and without deprotonation of propC. The Meta-F state of these variants displays low photochemical activity, but electronic excitation causes ultrafast alterations of the hydrogen bond network surrounding the chromophore. In all variants studied here, thermal back conversion from the photoproducts to Pfr is decelerated but substitution of His278 or Phe192 is not critical for the Pfr-to-Pr photoconversion. These variants do not impair deprotonation of propC or the α-helix/ß-sheet transformation of the tongue during the Meta-F-to-Pr decay. Thus, we conclude that propC deprotonation is essential for restructuring of the tongue.