Age-related learning difficulty through trial-and-error method associated with decreased default mode network integration in healthy middle-aged adults.

INTRODUCTION: Efficient learning is critical to adapting to different environments. There are well-known learning principles in cognitive rehabilitation, including errorless (EL) and trial-and-error (T&E) learning; however, little is known about their underlying neural mechanisms. In the current study, to understand the age-related changes in learning benefits and neural mechanisms applying EL and T&E learning methods in healthy middle-aged adults, we conducted a graph theoretical analysis using functional magnetic resonance imaging data and analyzed the relationship between learning benefits and age, as well as functional network connectivity and age, with both learning principles. METHOD: A total of 43 participants performed a color-name association task through EL and T&E learning methods. We focused on the functional connectivity patterns of the default mode network (DMN) since previous studies demonstrated this network to be more distinctive and important for the T&E learning method than EL. Within-network functional connectivity was used as the graph metric. RESULTS: Age showed significant moderate negative correlations with T&E scores and within-DMN functional connectivity in the test state following T&E learning. Conversely, age was not significantly correlated with EL scores or within-DMN functional connectivity in either the EL learning or test states. CONCLUSIONS: Our findings demonstrate the age-related learning decline associated with decreased DMN integration with aging, when applying the T&E method but not the EL method, even in healthy middle-aged adults. Relationships between the underlying neural network and age are different depending on the learning method. This suggests the need to take into consideration the remaining learning ability through the T&E learning method compared to normal aging and to utilize residual DMN functioning, in addition to the comparison between score differences between EL and T&E methods, when tailoring an individual learning approach.

Default mode network-associated intrinsic connectivity relates to individual learnability differences in errorless and trial-and-error learning.

The intrinsic functional network architecture accounts for task-evoked brain activity changes and variabilities in cognitive performance. Relationships between the intrinsic functional network architecture and task performance or learning ability have been previously reported. However, the relationships between learning benefits and the characteristics of intrinsic functional network architecture for different types of learning methods remain unclear. In this study, we used graph theoretical analysis to examine the relationships between intrinsic functional network connectivity and learning benefits in two well-known learning methods in the field of cognitive rehabilitation-errorless learning (EL learning) and trial-and-error learning (T&E learning). We focused on the default mode network (DMN) as a task-relevant network, which can differentiate between EL and T&E learning and was found to be more important for T&E learning in a previous study. Participants performed a color-name association task with both learning methods. The graph metrics used were within-network connectivity and efficiency for the DMN. Within-DMN connectivity and DMN efficiency showed a significantly weak positive correlation with T&E scores but not with EL scores. These findings show that the intrinsic integration strength within the DMN relates to individuals' learnability through the T&E method.

Spectral Properties of Chlorophyll f in the B800 Cavity of Light-harvesting Complex 2 from the Purple Photosynthetic Bacterium Rhodoblastus acidophilus.

The interactions of chlorophyll (Chl) and bacteriochlorophyll (BChl) pigments with the polypeptides in photosynthetic light-harvesting proteins are responsible for controlling the absorption energy of (B)Chls in protein matrixes. The binding pocket of B800 BChl a in LH2 proteins, which are peripheral light-harvesting proteins in purple photosynthetic bacteria, is useful for studying such structure-property relationships. We report the reconstitution of Chl f, which has the formyl group at the 2-position, in the B800 cavity of LH2 from the purple bacterium Rhodoblastus acidophilus. The Qy absorption band of Chl f in the B800 cavity was shifted by 14 nm to longer wavelength compared to that of the corresponding five-coordinated monomer in acetone. This redshift was larger than that of Chl a and Chl b. Resonance Raman spectroscopy indicated hydrogen bonding between the 2-formyl group of Chl f and the LH2 polypeptide. These results suggest that this hydrogen bonding contributes to the Qy redshift of Chl f. Furthermore, the Qy redshift of Chl f in the B800 cavity was smaller than that of Chl d. This may have arisen from the different patterns of hydrogen bonding between Chl f and Chl d and/or from the steric hindrance of the 3-vinyl group in Chl f.

Cognitive functions relating to aberrant interactions between task-positive and task-negative networks: Resting fMRI study of patients with schizophrenia.

Brain functional connectivity in the resting-state represents intrinsic functional states and correlates with cognitive performance. In patients with schizophrenia, reports on the relationships between forms of functional disconnectivity in local areas and cognitive disability have used resting-state functional magnetic resonance imaging data. Meanwhile, cognitive deficits in relation to inter-network forms of functional connectivity on a large scale are not well understood. This study examines cognitive functions in relation to the number of resting-state inter-network forms of functional connectivity focusing on task-positive networks (fronto-parietal network [FPN] and cingulo-opercular network [CON]) and task-negative network (default mode network [DMN]). We compare patients with schizophrenia (SCH group) and healthy controls (HC group). We conducted a functional network analysis by applying graph theory and evaluated cognitive functions using the Brief Assessment of Cognition in Schizophrenia. The number of forms of functional connectivity between FPN and DMN and between CON and DMN were significantly higher in SCH group than in HC group, and those in SCH group were also weakly correlated with their attention scores. It is suggested that fewer than typical functional segregations between task-positive and task-negative networks in SCH group relate to inefficient distribution of cognitive resources and low attentional abilities.

Excitation Energy Transfer from Bacteriochlorophyll b in the B800 Site to B850 Bacteriochlorophyll a in Light-Harvesting Complex 2.

Control of the spectral overlap between energy donors and acceptors provides insight into excitation energy transfer (EET) mechanisms in photosynthetic light-harvesting proteins. Substitution of energy-donating B800 bacteriochlorophyll (BChl) a with other pigments in the light-harvesting complex 2 (LH2) of purple photosynthetic bacteria has been extensively performed; however, most studies on the B800 substitution have focused on the decrease in the spectral overlap integral with energy-accepting B850 BChl a by reconstitution of chlorophylls into the B800 site. Here, we reconstitute BChl b into the B800 site of the LH2 protein from Rhodoblastus acidophilus to increase the spectral overlap with B850 BChl a. BChl b in the B800 site had essentially the same hydrogen-bonding pattern as B800 BChl a, whereas it showed a red-shifted Qy absorption band at 831 nm. The EET rate from BChl b to B850 BChl a in the reconstituted LH2 was similar to that of native LH2 despite the red shift of the Qy band of the energy donor. These results demonstrate the importance of the contribution of the density of excitation states of the B850 circular assembly, which incorporates higher lying optically forbidden states, to intracomplex EET in LH2.

Functional network activity during errorless and trial-and-error color-name association learning.

INTRODUCTION: In cognitive rehabilitation, errorless (EL) and trial-and-error (T&E) learning are well-known methods, but their neural mechanisms are not well known. In this study, we investigated functional magnetic resonance imaging data for healthy adults during EL and T&E learning. METHODS: Participants memorized color-name associations in both methods using Japanese traditional colors which were unfamiliar to study participants. A functional network analysis was conducted by applying graph theory. We focused on two major cognitive networks: the default mode network (DMN) and the fronto-parietal network (FPN). Also, we used "within-network connectivity" and "between-network connectivity" graph metrics. The former represents the functional connectivity strength of a subnetwork, namely the within-DMN connectivity and within-FPN connectivity, while the latter represents the number of links between the DMN and FPN. RESULTS: The within-DMN connectivity in T&E learning was significantly higher than in EL learning. The difference between the memory scores of EL and T&E learning weakly correlated with the between-network connectivity differences between both learning tasks. CONCLUSIONS: Our results suggest that within-DMN connectivity is important in T&E learning and that the learning benefit differences between EL and T&E approaches potentially relate to the functional integration strength between the DMN and FPN.

Reconstitution of 3-Acetyl Chlorophyll a into Light-Harvesting Complex 2 from the Purple Photosynthetic Bacterium Phaeospirillum molischianum.

The manipulation of B800 bacteriochlorophyll (BChl) a in light-harvesting complex 2 (LH2) from the purple photosynthetic bacterium Phaeospirillum molischianum (molischianum-LH2) provides insight for understanding the energy transfer mechanism and the binding of cyclic tetrapyrroles in LH2 proteins since molischianum-LH2 is one of the two LH2 proteins whose atomic-resolution structures have been determined and is a representative of type-2 LH2 proteins. However, there is no report on the substitution of B800 BChl a in molischianum-LH2. We report the reconstitution of 3-acetyl chlorophyll (AcChl) a, which has a 17,18-dihydroporphyrin skeleton, to the B800 site in molischianum-LH2. The 3-acetyl group in AcChl a formed a hydrogen bond with ß'-Thr23 in essentially the same manner as native B800 BChl a, but this hydrogen bond was weaker than that of B800 BChl a. This change can be rationalized by invoking a small distortion in the orientation of the 3-acetyl group in the B800 cavity by dehydrogenation in the B-ring from BChl a. The energy transfer from AcChl a in the B800 site to B850 BChl a was about 5-fold slower than that from native B800 BChl a by a decrease of the spectral overlap between energy-donating AcChl a and energy-accepting B850 BChl a.

Molecular Evolution and Functional Characterization of a Bifunctional Decarboxylase Involved in Lycopodium Alkaloid Biosynthesis.

Lycopodium alkaloids (LAs) are derived from lysine (Lys) and are found mainly in Huperziaceae and Lycopodiaceae. LAs are potentially useful against Alzheimer's disease, schizophrenia, and myasthenia gravis. Here, we cloned the bifunctional lysine/ornithine decarboxylase (L/ODC), the first gene involved in LA biosynthesis, from the LA-producing plants Lycopodium clavatum and Huperzia serrata We describe the in vitro and in vivo functional characterization of the L. clavatum L/ODC (LcL/ODC). The recombinant LcL/ODC preferentially catalyzed the decarboxylation of l-Lys over l-ornithine (l-Orn) by about 5 times. Transient expression of LcL/ODC fused with the amino or carboxyl terminus of green fluorescent protein, in onion (Allium cepa) epidermal cells and Nicotiana benthamiana leaves, showed LcL/ODC localization in the cytosol. Transgenic tobacco (Nicotiana tabacum) hairy roots and Arabidopsis (Arabidopsis thaliana) plants expressing LcL/ODC enhanced the production of a Lys-derived alkaloid, anabasine, and cadaverine, respectively, thus, confirming the function of LcL/ODC in plants. In addition, we present an example of the convergent evolution of plant Lys decarboxylase that resulted in the production of Lys-derived alkaloids in Leguminosae (legumes) and Lycopodiaceae (clubmosses). This convergent evolution event probably occurred via the promiscuous functions of the ancestral Orn decarboxylase, which is an enzyme involved in the primary metabolism of polyamine. The positive selection sites were detected by statistical analyses using phylogenetic trees and were confirmed by site-directed mutagenesis, suggesting the importance of those sites in granting the promiscuous function to Lys decarboxylase while retaining the ancestral Orn decarboxylase function. This study contributes to a better understanding of LA biosynthesis and the molecular evolution of plant Lys decarboxylase.

Characterization of the nitrate-nitrite transporter of the major facilitator superfamily (the nrtP gene product) from the cyanobacterium Nostoc punctiforme strain ATCC 29133.

The products of the NpR1527 and NpR1526 genes of the filamentous, diazotrophic, fresh-water cyanobacterium Nostoc punctiforme strain ATCC 29133 were identified as a nitrate transporter (NRT) and nitrate reductase (NR) respectively, by complementation of nitrate assimilation mutants of the cyanobacterium Synechococcus elongatus strain PCC 7942. While other fresh-water cyanobacteria, including S. elongatus, have an ATP-binding cassette (ABC)-type NRT, the NRT of N. punctiforme belongs to the major facilitator superfamily, being orthologous to the one found in marine cyanobacteria (NrtP). Unlike the ABC-type NRT, which transports both nitrate and nitrite with high affinity, Nostoc NrtP transported nitrate preferentially over nitrite. NrtP was distinct from ABC-type NRT also in its insensitivity to ammonium-promoted regulation at the post-translational level. The nitrate reductase of N. punctiforme was, on the other hand, inhibited upon addition of ammonium to medium, lending ammonium sensitivity to nitrate assimilation.