[Epidemiologic characteristics and influencing factors of influenza outbreaks in Guangdong Province, 2015-2022].

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.

[Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment].

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Ethnobotanical investigation of medicinal plants used in Lingchuan county, Shanxi, China.

Medicinal plants are the primary sources of healthcare among the people of developing countries in villages and local towns. Documenting and reporting the traditional knowledge of medicinal plants may contribute to pharmaceutical research development. For this reason, we present our findings on ethnomedicinal plants from Lingchuan County, Shanxi, China, an unexplored area rich in medicinal plant resources. Information of ethnomedicinal plants were collected through questionnaire/semi-structured interviews from 180 informants, including traditional healers. Field surveys were conducted in 53 villages of Lingchuan County from 2017 to 2018. Informed consent was obtained from each participant before conducting the interview process. Quantitative analysis was performed for each recorded species, such as Relative Frequency Citation (RFC), Use Value (UV), and Factor of Informant Consensus (FIC). Diseases were categorized into twelve groups. A total 138 species of medicinal plants were recorded, belonging to 123 genera of 58 families. Asteraceae was the dominant plant family with 19 species, followed by Rosaceae and Fabaceae. Herbs were dominant among plant life-forms with 96 species, followed by shrubs and trees (15 species each). Roots were the most commonly used plant parts with 58 species, followed by whole plants and fruits (28 species each). Most plant species were reported non-toxic (84, 60%), followed by unknown toxicity (35, 25%), poisonous, and less toxic (19, 14%). Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with a higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their FIC value, in which gynecological diseases have higher (0.93) FIC value followed by urinary system diseases. Most medicinal plants are used to clear away heat and relieve the surface. The present study revealed that local people of Lingchuan County confidently use ethnomedicinal plants for their healthcare needs. The higher indices value of a plant species resulted from quantitative analysis warrants further investigation, which may possess valuable phytochemical compounds that may result in new drugs for treating various human disorders.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

[Nutritional status predicts clinical outcomes in patients with gastric cancer undergoing radical gastrectomy].

Objective: To evaluate the effect of nutritional status on clinical and pathological data for stage Ⅰ-Ⅳ gastric cancer patients from the cancer survival investigation information. Methods: A database of 302 consecutive gastric cancer patients underwent radical gastrectomy was enrolled in this study. The clinical and pathological information of them were corrected and the relationship between the nutritional index and the patients survival time were analyzed by a Cox regression model. Results: The clinical data analysis of 302 patients with gastric cancer who received total gastric resection indicated that the nutritional status was related to the stage of tumor patients, suggesting that the later the stage was, the more necessary the nutritional therapy intervention was. Univariate analysis showed that Ⅲ+Ⅳ of TNM staging (HR=4.417, 95%CI:2.483-6.351; P =0.029), patient age of 65 and above (HR=2.217, 95%CI:0.522-3.912; P =0.038), lymph node metastasis positive (HR=2.517, 95%CI:0.516-4.518; P=0.036), poor tumor differentiation (HR=3.626, 95%CI:0.721-6.531; P =0.021) and low PNI (HR=2.612, 95%CI: 0.712-4.512; P =0.029) is an important risk factor for poor prognosis. In the multivariate analysis, Ⅲ+Ⅳ of TNM staging (HR=3.821, 95%CI:1.923-5.719; P =0.014), patient age of 65 and above (HR=1.168, 95%CI:0.321-2.015; P =0.036) and low PNI (HR=2.435, 95%CI:1.024-3.846; P =0.039) was independently correlated with poor survival time; When age was used as a stratification factor, the correlation between CONUT recurrence and survival in patients with gastric cancer ≥65 years old after total gastric resection was analyzed and compared. For disease-free survival, the CONUT high group (>3) was 25.2 months, while the CONUT low group (≤3) was 30.9 months, (χ2=3.763,P=0.029), showing a significant difference. For the overall survival, the CONUT high(>3) group was 30.3 months, compared with the CONUT low(≤3) group at 34.5 months, (χ2=4.924,P=0.042), and the difference was also statistically significant. Conclusions: High controlling nutritional status is an independent risk factor associated with poor gastric cancer survival and it is an independent risk factor in predicting overall survival (OS) in elderly (≥65) gastric cancer after radical gastrectomy.

Nutrient Contents in Tempe Produced from Five Cottage Industries in Selangor, Malaysia / Jurnal Sains Kesihatan Malaysia

@#This study aimed to determine the nutrient contents in tempe produced by five cottage industries in Selangor, Malaysia. Proximate contents were analysed by using standard methods of AOAC (1997) while carbohydrate content was calculated by difference. Mineral contents, total dietary fiber (TDF), total phenolic content and total isoflavone content were determined by Atomic Absorption Spectrophotometry (AAS), enzymatic-gravimetric (AOAC 985.29), Folin-Ciocalteu colorimetric and High Performance Liquid Chromatography (HPLC) respectively. Macronutrients were reported in 100 g sample and the results showed the average nutrient contents were as follow: 63.07 ± 3.18% moisture, 19.63 ± 1.50% protein, 0.65 ± 0.17% fat, 0.70 ± 0.06% ash and 15.95 ± 1.88% total carbohydrate. The average mineral content in 100 g samples (based on wet basis) were 29.45 ± 5.67 mg calcium, 13.28 ± 5.76 mg magnesium, 3.48 ± 1.09 mg sodium and 2.06 ± 0.33 mg ferum. The results showed that the average of TDF content was 8.05 ± 3.65%. Total phenolic content was 259.87 ± 22.62 mg of GAE/g. The total isoflavone content in 100 g samples (wet basis) was 41.94 ± 10.42 mg/100 g. This study had shown that total phenolic content was significantly correlated (p < 0.01) with total isoflavone content in all tempe samples. It can be concluded that there was no significant difference (p > 0.05) in nutrient contents among tempe samples produced by five cottage industries located in Selangor, Malaysia. However, the mineral and isoflavone contents in the present study were lower compared to previous studies.

Clinical manifestations and radiological features may contribute to the early diagnosis of radiation-induced sarcoma after breast cancer.

AIM: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer. MATERIALS AND METHODS: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides. RESULTS: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy. CONCLUSIONS: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected.

Postural sway and perception of affordances in children at risk for developmental coordination disorder.

Gibson (The ecological approach to visual perception, Houghton Mifflin, Boston, 1979/1986) defined affordances as opportunities for motor behaviors, and highly emphasized the interaction between perception and action. Research on children with developmental coordination disorder commonly reports difficulties in judgments of affordances (perception) and in postural control (action). However, how perception and action are coupled has not been studied yet. The present study sought to evaluate the relationship between control of postural sway and perception of affordances in children at risk for developmental coordination disorder (RDCD) and typically developing children (TDC). We hypothesized that the relationship between perception and action would differ between groups. Participants made a series of judgments about their maximum sitting height (SHmax) while standing with and without wearing 10 cm blocks on feet. Postural sway and the judgment accuracy were recorded. Our findings showed that RDCD swayed more during judgment sessions and made less accurate judgments compared to TDC. In addition, TDC reduced postural sway from inter-judgment to judgment sessions, whereas the postural sway of RDCD remained identical between sessions. Last, while TDC reduced postural sway across judgment trials and revealed a learning effect of the judgments about SHmax in the block condition, RDCD never modulated postural sway and did not learn their SHmax in both non-block and block conditions. Overall, modulation of postural sway differed between groups during judgment sessions and between inter-judgment and judgment sessions, whereby their perceptual judgments about SHmax were differentially influenced. To summarize, this study demonstrated a difference in perception and action coupling between RDCD and TDC.

Dual-task study of cognitive and postural interference: a preliminary investigation of the automatization deficit hypothesis of developmental co-ordination disorder.

BACKGROUND: The purpose of this study was to investigate whether children with developmental co-ordination disorder and balance problem (DCD-BP) had greater problems than controls in performing a primary balance task while concurrently completing different cognitive tasks varying in oral or listening cognitive complexity, as well as to investigate the automatization deficit hypothesis of DCD-BP. METHODS: Children with DCD-BP (n= 39), along with age-matched control counterparts (n= 39), were placed on automatic processing situation under dual-task conditions. All children were required to perform a primary task, five dual-task paradigms (oral counting task, auditory-verbal reaction task, auditory-choice reaction task, auditory-memory task and articulation alone) and an eyes-closed balancing task. RESULTS: In the primary task condition, the differences were not statistically significant (P= 0.393) between children with and without DCD-BP. However, children with DCD-BP were significantly more impaired on three of five dual-task conditions (oral counting task: P= 0.003; auditory-verbal reaction task: P= 0.011; auditory-memory task: P= 0.041) compared with the single-task situation, with the exception of the auditory-choice reaction task (P= 0.471) and articulation alone (P= 0.067). CONCLUSIONS: These results suggest that children with DCD-BP were more cognitively dependant and may have an automatization deficit.

The prevalence and distribution of bone defects in patients with moderate to advanced periodontitis.

BACKGROUND: Alveolar bone defect is one of the common features of periodontitis and may vary in its form, extent, and distribution among teeth and individuals. The purpose of this study was to analyze the prevalence and distribution of different forms of bone defects in Taiwanese patients with moderate to advanced periodontitis. METHODS: One hundred and thirty-seven Taiwanese patients with moderate to advanced periodontitis comprising a total sample of 3542 teeth were studied. During periodontal surgery, osseous defects were explored and classified as interproximal crater, 1-wall, 2-wall, 3-wall, hemiseptal and circumferential defects. Among them, some were also recorded as complicated defects. RESULTS: Among 3542 existing teeth, 1376 were examined surgically and 483 teeth had bone defects. There was an increase in bone defects from anterior to posterior. The frequencies of defects in anterior and posterior segments were significantly different. More defects were found on the right side than on the left side. Yet there was no difference between the maxillary and mandibular arch. Interproximal surfaces of the first and second molars had the highest prevalence of bone defects. Crater was the most common defect type (26.50%), followed by circumferential (23.40%) and 3-wall defect (20.08%). More than 40% also presented with complicated defects. CONCLUSIONS: There was an increase in bone defects from anterior to posterior. Interproximal aspects were more frequently involved than buccal or lingual aspects. Crater, circumferential and 3-wall defects were more common than other defect types. The treatment of complicated defects, which comprise over 40% of all defects, presents a challenging task for periodontists.

Classifiers and social control in wheelchair rugby.

The purpose of this study was to examine the features of wheelchair rugby classifiers in order to maintain social control in wheelchair rugby. The examination centered on the theme-resources used by classifiers to maintain the authority of International Wheelchair Rugby Federation (IWRF). Data were collected using participant observation methodology at national and international wheelchair rugby championships and a survey of the 14 IWRF authorized classifiers. The results of this study identified five essential features of IWRF classifiers. In particular, they need to have a background in medicine or physical therapy. In addition, IWRF classifiers use their medical and sporting knowledge and experience to control the wheelchair rugby classification process and to maintain fairness of competition. The results of this study may help to train Taiwanese professionals with medical or sporting backgrounds to become international classifiers and also to develop appropriate training programs for national classifiers.

Comparison of ball-and-racquet impact force between two tennis backhand stroke techniqes.

STUDY DESIGN: A mixed design for kinetic comparison of 2 types of one-handed backhand strokes and 2 skill levels in tennis. OBJECTIVES: To develop and evaluate a model to estimate the impact force on the racquet during tennis stroke, and to compare the peak impact force between one-handed backhand stroke with a long backswing and one-handed backhand stroke with a short backswing and between the beginning and advanced players. BACKGROUND: A one-handed backhand stroke is commonly used in tennis and may be associated with many upper extremity over-use injuries. An understanding of kinetics of the backhand stroke is essential for understanding injury mechanisms and prevention. METHODS AND MEASURES: Five male advanced tennis players and 4 male and 1 female beginning tennis players participated. Mean age was 32.2 +/- 7.0 years. Each subject was instructed to use the 2 types of one-handed backhand strokes to hit balls from a tennis ball machine. Three-dimensional coordinates of critical body and racquet landmarks were obtained. A mathematical model was developed to estimate the contact duration and the peak impact force during a stroke. RESULTS: The estimated peak impact forces were reproducible and comparable to those reported in the literature from direct measurements. A one-handed backhand stroke with a short backswing had a significantly shorter contact duration (0.008 +/- 0.003 seconds) and a greater peak resultant impact force (330.0 +/- 140.7) than that with a long backswing (0.016 +/- 0.004 seconds and 180.8 +/- 49.1 N). Skill level did not significantly affect the peak resultant impact force. CONCLUSION: A long backswing in a one-handed backhand stroke may reduce the load on the upper extremity and may assist in reducing the risks of tennis-related upper extremity over-use injuries.

Factors influencing sport participation among athletes with spinal cord injury.

OBJECTIVE: This exploratory study examined the relationships between pre- and post-injury sport participation among active individuals with spinal cord injury (SCI) in the United Kingdom. In particular, factors that influence individuals with SCI into sport were identified. METHODS: A total of 143 British individuals with SCI currently participating in wheelchair basketball, wheelchair rugby, wheelchair tennis, and wheelchair athletics were recruited. A total of 112 subjects were active prelesion, and 31 subjects were inactive preinjury. A Disability Sport Participation questionnaire developed by the authors was used for data collection. The questionnaire was distributed through the British Wheelchair Sport Associations. Personal, impairment, health and fitness, socialization, and participation data of athletes with SCI were collected. Groups of active preinjury and inactive preinjury were compared. RESULTS: For athletes who had been active pre-SCI, the in-hospital rehabilitation program and specialized sport club for people with disabilities were more important contexts for introducing the sport after injury to individuals. Friends and peers with disabilities were much more influential as initial and continuing socialization agents than rehabilitation therapists. The main reasons for athletes with SCI who participated in sports after injury were for fitness, fun, health, and competition, although many athletes noted that social aspects and rehabilitation also influenced their sport participation. CONCLUSION: This study identified social contexts, social agents, difficulties, sources of information, and reasons for sport participation of athletes with SCI. The results may offer some directions for the improvement of rehabilitation programs for people with SCI and also help the development of appropriate strategies to encourage people with SCI to participate in sports and leisure activities.

Biopharmaceutics of transmucosal peptide and protein drug administration: role of transport mechanisms with a focus on the involvement of PepT1.

Non-invasive delivery of peptide and protein drugs will soon become a reality. This is due partly to a better understanding of the endogenous transport mechanisms, including paracellular transport, endocytosis, and carrier-mediated transport of mucosal routes of peptide and protein drug administration. This paper focuses on work related to the elucidation of structure-function, intracellular trafficking, and regulation of the intestinal dipeptide transporter, PepT1.

Molecular role for the Rab binding platform of guanine nucleotide dissociation inhibitor in endoplasmic reticulum to Golgi transport.

Guanine nucleotide dissociation inhibitor (GDI) regulates the recycling of Rab GTPases involved in vesicle targeting and fusion. We have analyzed the requirement for conserved amino acid residues in the binding of Rab1A and the function of GDI in transport of cargo between the endoplasmic reticulum (ER) and the Golgi apparatus. Using a new approach to monitor GDI-Rab interactions based on the change in fluorescence associated with the release of methylanthraniloyl guanosine di(tri)phosphate-GDP (mGDP) from Rab, we show that residues previously implicated in the binding of the synapse-specific Rab3A, including Gln-236, Arg-240, and Thr-248, are essential for the binding of Rab1A. Mutation of each of these residues has potent effects on the ability of GDI to remove Rab1A from membranes and inhibit ER to Golgi transport in vitro. Given the sequence divergence between Rab1A and 3A (35% identity), these residues are proposed to play a general role in GDI function in the cell. In contrast, several other residues found within or flanking the Rab-binding region were found to have differential effects in the recognition and recycling of Rab1A and 3A, and therefore direct selective interaction of GDI with individual Rab proteins. Intriguingly, mutation of one residue, Arg-70, led to a reduction of Rab1A binding, failed to extract Rab1A from membranes in vitro, yet bound membranes tightly and potently inhibited ER to Golgi transport. These results provide evidence that novel membrane-associated factor(s) mediate Rab-independent GDI interaction with membranes.

Molecular identification of a role for tyrosine 167 in the function of the human intestinal proton- coupled dipeptide transporter (hPepT1).

hPepT1 is a proton-coupled peptide transporter that mediates the absorption of di- and tripeptides. Here we show that tyrosine 167 (Y167) in transmembrane domain 5 (TMD5) of this 12-transmembrane spanning protein contributes to its transport function. We identified this particular amino acid by a computer model of the arrangement of the TMDs of hPepT1 and investigated its role by site-directed mutagenesis and dipeptide uptake studies. [3H]Gly-sar uptake in cells transiently transfected with Y167A-hPepT1 was abolished completely, even though the level of Y167A-hPepT1 expression by Western blot analysis and cell surface expression by immunofluorescence microscopy was similar to those of the wild type. Therefore, mutation affected transport function, but apparently not the steady-state protein level or trafficking of the transporter to the plasma membrane. Moreover, mutation of Y167 into phenylalanine, serine, or histidine all abolished gly-sar uptake in transfected HEK 293 cells. Taken together, these findings suggest that Y167 plays an essential role in hPepT1 function, perhaps due to the unique chemistry of its phenolic side chain.

Mutations in GDI1 are responsible for X-linked non-specific mental retardation.

Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that play an essential role in the recycling of Rab GTPases required for vesicular transport through the secretory pathway. We have found mutations in the GDI1 gene (which encodes uGDI) in two families affected with X-linked non-specific mental retardation. One of the mutations caused a non-conservative substitution (L92P) which reduced binding and recycling of RAB3A, the second was a null mutation. Our results show that both functional and developmental alterations in the neuron may account for the severe impairment of learning abilities as a consequence of mutations in GDI1, emphasizing its critical role in development of human intellectual and learning abilities.