IMiD/CELMoD-induced growth suppression of adult T-cell leukemia/lymphoma cells cereblon through downregulation of target proteins and their downstream effectors.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasia associated with human T-cell leukemia virus type 1 (HTLV-1) infection and has an extremely poor prognosis. Lenalidomide (LEN; a second-generation immunomodulatory drug [IMiD]) has been employed as an additional therapeutic option for ATL since 2017, but its mechanism of action has not been fully proven, and recent studies reported emerging concerns about the development of second primary malignancies in patients treated with long-term IMiD therapy. Our purpose in this study was to elucidate the IMiD-mediated anti-ATL mechanisms.

Infants' Prefrontal Hemodynamic Responses and Functional Connectivity During Joint Attention in an Interactive-Live Setting.

The present study examined cerebral hemodynamic responses and functional connectivity during joint attention either initiated by infants (Initiating Joint Attention, IJA condition) or by their partner (Responding to Joint Attention, RJA condition). To capture responses to natural social cues in infants aged 7-12 months using functional near-infrared spectroscopy (fNIRS), we employed an interactive-live paradigm for IJA and RJA. During the measurement, an adult sat facing an infant, and objects, such as small stuffed animals, paired with sound toys were presented to the right or left side of the screen.

Exploring factors of successful transition to elementary school among children with autism spectrum disorder in Japan: a focus group study.

: Children with autism spectrum disorder (ASD) face numerous challenges in transitioning to elementary school, which can cause confusion for the children and concern among their parents. : This study aimed to identify the process of school transition from kindergarten to elementary school for children with autism spectrum disorder in Japan, by evaluating the effectiveness of a school transition program. : A focus group interview was conducted with seven parents who participated in a transition program.

Modeling Training of Child's Echoic Conversational Response for Students with Autism Spectrum Disorder: To Be a Good Listener.

Students with autism spectrum disorder (ASD) often have difficulties in responding to conversation with verbal language. These students often repeat what they hear, and their echoic behavior has a potentially communicative function. We define the echoic behavior when an individual repeats a peer's topic word with appropriate prosody within 3 s as the .

Sentence Reading Comprehension by Means of Training in Segment-Unit Reading for Japanese Children with Intellectual Disabilities.

Children with intellectual disabilities (ID) often have difficulty in sentence reading and comprehension. Previous studies have shown that training in segment-unit reading (SUR) facilitates the acquisition of sentence reading comprehension skills for Japanese students with ID. However, it remains unknown whether SUR training is also effective for individuals unable to read sentences and can generalize to untrained sentences.

Social interaction facilitates word learning in preverbal infants: Word-object mapping and word segmentation.

In natural settings, infants learn spoken language with the aid of a caregiver who explicitly provides social signals. Although previous studies have demonstrated that young infants are sensitive to these signals that facilitate language development, the impact of real-life interactions on early word segmentation and word-object mapping remains elusive. We tested whether infants aged 5-6 months and 9-10 months could segment a word from continuous speech and acquire a word-object relation in an ecologically valid setting.

Contingent imitation increases verbal interaction in children with autism spectrum disorders.

Several studies have suggested that contingent adult imitation increase nonverbal communication, such as attention and proximity to adults, in children with autism spectrum disorders. However, few studies have shown the effect of contingent imitation on verbal communication. This study examined whether children with autism were able to promote verbal interaction such as vocal imitation, vocalization, and vocal turn-taking via contingent imitation.

"Mom called me!" Behavioral and prefrontal responses of infants to self-names spoken by their mothers.

Development of a sense of self is a fundamental process needed for human social interaction. Although functional neuroimaging studies have revealed the importance of medial prefrontal cortex (mPFC) in self-referencing, how this function develops in infancy remains poorly understood. To determine the cerebral basis underlying processing of self-related stimuli, we used behavioral measures and functional multi-channel near-infrared spectroscopy (fNIRS) to measure prefrontal cortical responses in 6-month-old infants hearing their own names.

Motor cortex-evoked activity in reciprocal muscles is modulated by reward probability.

Horizontal intracortical projections for agonist and antagonist muscles exist in the primary motor cortex (M1), and reward may induce a reinforcement of transmission efficiency of intracortical circuits. We investigated reward-induced change in M1 excitability for agonist and antagonist muscles. Participants were 8 healthy volunteers.

Stimulus pairing training for Kanji reading skills in students with developmental disabilities.

Japanese students with developmental disabilities often exhibit difficulties in reading, particularly in Kanji (ideogram) reading, and in acquiring the equivalence relations between pictures, written words, and sounds. Previous research suggested that one student with autism could acquire Kanji reading along with equivalence relations through stimulus pairing training. However, maintenance rates tended to be very low, possibly due to the lack of picture stimuli.

Predicting recovery of cognitive function soon after stroke: differential modeling of logarithmic and linear regression.

Cognitive disorders in the acute stage of stroke are common and are important independent predictors of adverse outcome in the long term. Despite the impact of cognitive disorders on both patients and their families, it is still difficult to predict the extent or duration of cognitive impairments. The objective of the present study was, therefore, to provide data on predicting the recovery of cognitive function soon after stroke by differential modeling with logarithmic and linear regression.

Reciprocal changes in input-output curves of motor evoked potentials while learning motor skills.

Reciprocal inhibition of antagonist muscles is crucial for motor skill learning in humans. However, the changes in reciprocal inhibition function during the motor learning process are unknown. The aim of this study was to systematically observe the changes in reciprocal inhibition function.

Cerebral responses to infant-directed speech and the effect of talker familiarity.

A number of behavioral studies suggest that infant-directed speech (IDS) plays a more important role in facilitating both: a) speech perception, and b) adult-infant social interactions than does adult-directed speech (ADS), and hence that IDS contributes to subsequent social and language development. However neural substrates that may underlie these IDS functions have not been examined. The present study examined cerebral hemodynamic responses to IDS in 48 infants (4-13 months of age) using near-infrared spectroscopy (NIRS).

Comparative analysis of human SRC-family kinase substrate specificity in vitro.

Src family kinases (SFKs) are the earliest known family of tyrosine kinases and are widely thought to play essential roles in cellular signal transduction. Although numerous functional analyses have been performed, no study has analyzed the specificity of all SFKs on an equal platform. To gain a better understanding of SFK phosphorylation, we designed a high-throughput in vitro kinase assay on the subproteome scale using surface plasmon resonance.

Identification and functional analyses of 11,769 full-length human cDNAs focused on alternative splicing.

We analyzed diversity of mRNA produced as a result of alternative splicing in order to evaluate gene function. First, we predicted the number of human genes transcribed into protein-coding mRNAs by using the sequence information of full-length cDNAs and 5'-ESTs and obtained 23 241 of such human genes. Next, using these genes, we analyzed the mRNA diversity and consequently sequenced and identified 11 769 human full-length cDNAs whose predicted open reading frames were different from other known full-length cDNAs.

Cerebral laterality for phonemic and prosodic cue decoding in children with autism.

This study examined the cerebral functional lateralization, from a phonological perspective, in children with autism spectrum disorder (ASD) and typically developing children (TDC). With near infrared spectroscopy, we measured auditory evoked-responses in the temporal areas to phonemic and prosodic contrasts in word contexts. The results of TDC showed stronger left-dominant and right-dominant responses to phonemic and prosodic differences, respectively.

Human Gene and Protein Database (HGPD): a novel database presenting a large quantity of experiment-based results in human proteomics.

Completion of human genome sequencing has greatly accelerated functional genomic research. Full-length cDNA clones are essential experimental tools for functional analysis of human genes. In one of the projects of the New Energy and Industrial Technology Development Organization (NEDO) in Japan, the full-length human cDNA sequencing project (FLJ project), nucleotide sequences of approximately 30 000 human cDNA clones have been analyzed.

Human protein factory for converting the transcriptome into an in vitro-expressed proteome,

Appropriate resources and expression technology necessary for human proteomics on a whole-proteome scale are being developed. We prepared a foundation for simple and efficient production of human proteins using the versatile Gateway vector system. We generated 33,275 human Gateway entry clones for protein synthesis, developed mRNA expression protocols for them and improved the wheat germ cell-free protein synthesis system.

Functional training for initiating joint attention in children with autism.

The present study aimed to examine the controlling variables for initiating joint attention (IJA) in three children with autism. During the baseline, target objects were presented in a location where the child could see them, but the adult could not, and the emergence of IJA was assessed. Children with autism showed some IJA skills during the baseline, but none initiated pointing.

Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs).

Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability.

Several previous studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence.

Complete sequencing and characterization of 21,243 full-length human cDNAs.

As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding.

Role of primary sensorimotor cortex and supplementary motor area in volitional swallowing: a movement-related cortical potential study.

We investigated the role of the cerebral cortex, particularly the face/tongue area of the primary sensorimotor (SMI) cortex (face/tongue) and supplementary motor area (SMA), in volitional swallowing by recording movement-related cortical potentials (MRCPs). MRCPs with swallowing and tongue protrusion were recorded from scalp electrodes in eight normal right-handed subjects and from implanted subdural electrodes in six epilepsy patients. The experiment by scalp EEG in normal subjects revealed that premovement Bereitschaftspotentials (BP) activity for swallowing was largest at the vertex and lateralized to either hemisphere in the central area.

Computer-based sorting-to-matching in identity matching for young children with developmental disabilities.

We evaluated a computer-based sorting-to-matching procedure to teach matching-to-sample skills to seven young children with developmental disabilities who had failed to demonstrate identity matching-to-sample under the typical training procedure (such as observing a sample then selecting a comparison stimulus). In the sorting-to-matching procedure, rather than clicking on a comparison stimulus, the children moved the sample stimulus under the identical comparison stimulus. For all the children, identity matching-to-sample accuracy rapidly increased when the sorting-to-matching procedure was introduced, while it remained at chance levels in the typical training procedure.