Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Requirements for the Recruitment of Gaa1 into a Functional Glycosylphosphatidylinositol Transamidase Complex*

Glycosylphosphatidylinositol (GPI)-anchored proteins are synthesized on membrane-bound ribosomes, translocated across the endoplasmic reticulum membrane, and GPI-anchored by GPI transamidase (GPIT). GPIT is a minimally heterotetrameric membrane protein complex composed of Gaa1, Gpi8, PIG-S and PIG-T. We describe structure-function analyses of Gaa1, the most hydrophobic of the GPIT subunits, with the aim of assigning a functional role to the different sequence domains of the protein. We generated epitope-tagged Gaa1 mutants and analyzed their membrane topology, subcellular distribution, complex-forming capability, and ability to restore GPIT activity in Gaa1-deficient cells. We show that (i) detergent-extracted, Gaa1-containing GPIT complexes sediment unexpectedly rapidly at ∼17 S, (ii) Gaa1 is an endoplasmic reticulum-localized membrane glycoprotein with a cytoplasmically oriented N terminus and a lumenally oriented C terminus, (iii) elimination of C-terminal transmembrane segments allows Gaa1 to interact with other GPIT subunits but renders the resulting GPIT complex nonfunctional, (iv) interaction between Gaa1 and other GPIT subunits occurs via the large lumenal domain of Gaa1 located between the first and second transmembrane segments, and (v) the cytoplasmic N terminus of Gaa1 is not required for formation of a functional GPIT complex but may act as a membrane-sorting determinant directing Gaa1 and associated GPIT subunits to an endoplasmic reticulum membrane domain.
Effet de la position de la syllabe sur la réalisation acoustique des consonnes finales du thaï

De nombreuses études ont montré les différences dans les réalisations acoustiques des consonnes en fonction de leur position dans le mot. Ce travail compare les caractéristiques acoustiques des consonnes finales de syllabes identiques du thaï dans les différentes positions. Ces consonnes se trouvent soit devant une frontière de mot CVC#CVC, soit devant une frontière de syllabe à l’intérieur d’un mot dissyllabique CVC.CVC. L’objectif est de savoir si le type de frontière (inter-mots vs . intra-mot) a un effet sur la réalisation de ces consonnes. Les premiers résultats montrent que non seulement la durée de la consonne finale mais aussi celle de la voyelle précédente et celle de la syllabe sont significativement influencées par le type de frontière. D’autres paramètres acoustiques sont en cours d’analyse. Il s’agit d’une étape préliminaire à une étude ayant pour but de comprendre les caractéristiques de la langue source (le thaï) susceptibles d’être des éléments pouvant empêcher l’acquisition des consonnes finales de la langue cible (le français). Effects of syllable position on the acoustic realization of Thai final consonants Various studies have shown differences in the acoustic realization of consonants as a function of their position in the word. This paper presents an acoustical study of Thai final consonants in identical syllables, in relation to the types of boundary (before a word boundary CVC#CVC or before a syllable boundary CVC.CVC). The aim of this study is to understand if the boundary type (inter-words vs . intra-word) has an effect on the realization of these final consonants. The very first results show that not only the duration of the final consonants but also those of the preceding vowel and of the syllable are significantly affected by the types of boundary. Further acoustical parameters are currently being analyzed. It is a preliminary step to study and understand which characteristics of the source language potentially acting as a phonological sieve to the acquisition of French final consonants.
The hybridoma revolution: an offshoot of basic research.

In this narrative, I describe how my interest in the nature and origin of antibody diversity led me to tackle the problem by using somatic cell genetic techniques. The first hybridoma (an immortal antibody-secreting cell line derived by fusion of a short-lived lymphocyte and a myeloma cell line) was an offshoot of this approach. Although not intended for such purposes, it soon became obvious that this invention had widespread potential in basic research and industry. Indeed, the technique opened new inroads into the study of complex biological substances and became the method of choice to define new differentiation markers. Hybridomas also allowed us to dissect the immune response to a simple antigen and to demonstrate the critical role of somatic mutations in the generation of high affinity antibodies. Now, monoclonal antibodies can be derived and manipulated in vitro, leading to important new developments in therapeutic applications. BioEssays 1999;21:966-973.
The neural interaction between the arterial baroreflex and muscle metaboreflex is preserved in older men

• What is the central question of this study? Sympathetic baroreflex sensitivity increases during isolated skeletal muscle metaboreflex activation in young adults, but whether this neural interaction between the arterial baroreflex and the muscle metaboreflex is altered in healthy ageing remains unclear. • What is the main finding and its importance? The collective findings indicate that the neural interaction between the arterial baroreflex and the skeletal muscle metaboreflex in the regulation of muscle sympathetic nerve activity is preserved in healthy ageing. This has potential implications for the regulation of blood pressure during exercise in older adults.
Phenotypic Differences in Normal vs High Tension Glaucoma

Background: Normal tension glaucoma (NTG) and high tension open angle glaucoma (HTG) are associated with characteristic patterns of optic nerve findings and corresponding patterns of visual field loss. In the past, clinicians viewed NTG and HTG as distinct entities, with separate underlying pathophysiologies and often different clinical presentations and courses. Methods: Literature review. Results: Optic nerve and visual field findings in NTG have been reported to be dissimilar to those in HTG. In more recent years, however, there has been increasing recognition of the shared features NTG and HTG. Conclusion: There is now a trend to consider these two entities as part of a spectrum of glaucoma with overlapping pathophysiology and clinical characteristics.
Effect of oral contraceptives on respiratory function.

The present study was carried out to assess the lung functions in oral contraceptive administered women. Lung function tests were carried out with Spirometer (Vitallograph Compact II). A significant increase in vital capacity (VC) was observed in these women as compared to normal control. There was also a significant decrease in forced expiratory volume in 1 sec. /vital capacity (FEV1/VC%) and forced expiratory volume in 1 sec. /forced vital capacity (FEV1/FVC%) among oral contraceptive administered women as compared to controls. Further, a significant increase in peak expiratory flow rate (PEF), reduction in forced expiratory flow rate (FEF75-85%) and FEF75% were observed among oral contraceptive administered women as compared to controls. The increase in VC and PEF might be due to the synthetic form of progesterone (progestins) present in oral contraceptive pills which causes hyperventilatory changes. Synthetic progesterone during luteal phase of menstrual cycle might increase the static and dynamic volumes of lung i.e. VC and PEF. But FEF75% showed a decrease which might be due to the lower neuromuscular coordination during breathing.
Gut Microbiota Composition Is Related to AD Pathology

Introduction Several studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Materials and Methods We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE. Results The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp. , Lachnospiraceae spp. , Marvinbryantia spp. , Monoglobus spp. , [Ruminococcus] torques group spp. , Roseburia hominis, and Christensenellaceae R-7 spp. , was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp. , Lachnoclostridium spp. , Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status. Conclusions Gut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.
Metabolic effects on growth and muscle of soya-bean protein feeding in cod (Gadus morhua)

The aim of the present study was to investigate the effect of soya-bean protein on growth and muscle metabolism in fish. Cod, Gadus morhua, were fed on a fish-feed formula with the high-quality fish-meal protein being replaced by 100, 200 or 300 g soya-bean protein/kg fish-meal protein. The feeding experiment lasted for 43 d at a water temperature of 7–8º and a sea water salinity of 3.5%. At the 200 g/kg level of soya-bean protein, food intake and growth rate were similar to those of the controls. At the 300 g/kg level of soya-bean protein, food intake was diminished by 6 % and growth by 67 % relative to control levels. In muscle, sarcoplasmic protein (/g wet weight) was significantly decreased by 14%. Myofibrillar protein (/g wet weight) was unchanged. Levels of RNA in the myofibrillar fraction decreased at all three levels of soya-bean protein, and that of the sarcoplasmic fraction decreased at the highest level of legume-protein. With increased levels of soya-bean protein, RNA: DNA declined by 18% from 1.88 to 1.54. The contractile protein myosin heavy chain (/mg protein and /g wet weight) and myosin heavy chain-specific mRNA (/mg RNA) were not significantly affected by dietary conditions. Expressed per g wet weight, the decline by 21 % of the specific mRNA depended on the total RNA content which decreased with the increase in soya-bean protein. Acid proteinase activity was lowest at the 200 g/kg level, showing a decrease of 23%. Glycogen content fell by 46% at both the 200 and 300 g/kg level of dietary soya-bean protein. The results show that muscle metabolic functions responded to the dietary plant protein before there were any measurable changes in growth rate. From the results it is concluded that 200 g/kg or less of the high-quality fish-meal protein may be replaced by soya-bean protein in a fish-feed formula.
The Fractionation of Arithmetical Skills: A Single Case Study

A single case study of a patient with a selective impairment of arithmetical calculation is reported. DRC became severely acalculic after sustaining a left parietal intra-cerebral haematoma. His numeracy skills were documented as fully as possible. It was found that his knowledge of the significance of individual numbers and his concept of quantity appeared to be intact, but simple addition, subtraction and multiplication were all performed laboriously and inaccurately and his performance was inconsistent from trial to trial. Further it was shown that it was his knowledge of arithmetical facts not his knowledge of arithmetical operations which was impaired. The findings are discussed in relation to models of arithmetical calculation and it is concluded that for DRC there was a deficit in accessing one category of verbal semantic knowledge systems, namely arithmetical facts.
Clostridium Diffi cile-Associated Diarrhea in a Pediatric Hospital

This retrospective cohort analysis examined the risk factors, symptoms, and severity of disease associated with C. difficile in pediatric inpatients. Risk factors for a C. difficile-positive test were an oncologic diagnosis, diarrhea of more than 2 days' duration, and gastrointestinal symptoms, especially abdominal pain. Over a 3.5-year period, there was a total of 22 C. difficile-positive patients, and most had mild, self-limiting diarrheal illness. No cases of C. difficile diarrhea were identified. Seventy-eight percent of the C. difficile-positive patients were found to have alternate risk factors for diarrhea. Our data indicate that C. difficile rarely causes severe diarrhea in pediatric inpatients and that C. difficile testing should be limited to patients with severe prolonged diarrhea and abdominal pain.
The evaluation of dysphonia for Cantonese school-age children : a multiparametric approach

The present study investigated the feasibility of using multiparametric approach to predict the presence of dysphonia in Cantonese school-age children. A total of 30 children (16 dysphonic and 14 control) aged 6;02 to 12;07 participated in the study. The voice of each child was recorded and evaluated acoustically, aerodynamically, and using voice range profiles. A minimal set of instrumental voice parameters was identified based on the predictive power of each parameter in discriminating dysphonic and normal voices. Results showed that the two groups performed significantly differently in six parameters, including relative average perturbation, shimmer percent, maximum phonation time, mean airflow rate, intensity range and profile area in voice range profile. The combined use of shimmer percent and maximum phonation time correctly predicted 93.33% of the voices. These results agreed with many previous studies, indicating the value of clinical use and further investigation of multiparametric approach in evaluating voice quality in children.
Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma

Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples. TP53 R181C, KRAS G12C and SMAD4 R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3+ regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.
Tyrosine phosphorylation during synapse formation between identified leech neurons.

1. We have examined whether tyrosine phosphorylation is required for synapse formation between identified neurons from the central nervous system of the leech in culture. 2. Within a few hours of contact with the cell body of the serotonergic Retzius neuron (R cell), the soma of the postsynaptic pressure‐sensitive neuron (P cell), but not the R cell, could be labelled intracellularly with an antibody against phosphotyrosine residues. The labelling seemed specific for P cells contacted by R cells, as it was greatly reduced in pairs of either R or P cells and in single cells. Genistein (20 microM) and lavendustin A (10 microM), selective inhibitors of tyrosine kinases, blocked the labelling of contacted P cells, whereas their ineffective analogues (genistein and lavendustin B) had no effect on labelling. 3. R cell contact also induced the loss of an extrasynaptic, depolarizing response (due to modulation of cation channels) to serotonin (5‐HT) in the P cell within a few days of juxtaposing cell bodies and within an hour of contact with growth cones. Treatment of the neurons with the tyrosine kinase inhibitors (but not the ineffective analogues) prevented the loss of the depolarizing response and of single cation channel modulation by 5‐HT. 4. R cells formed inhibitory, Cl(‐)‐dependent synapses with P cells. Synapse formation was prevented by the tyrosine kinase inhibitors but not by their ineffective analogues. These compounds had no obvious effect on neurite outgrowth or cell adhesion. We conclude that tyrosine phosphorylation is a signal during the formation of this synapse.
Development of modified force field for cation-amino acid interactions: Ab initio-derived empirical correction terms with comments on cation- interactions

The modeling of voltage-gated ion-channel proteins is a continuing challenge for force-field calculations because of the diverse range of interactions involved. In particular, current force fields are not parameterized for either ion]amino acid or amino acid]electric field interactions. To address the parameterization of ion]amino acid interactions, we have tested the use of empirical correction terms, derived from ab initio calculations of single amino Ž . q acids representing the peptide backbone interacting with K ions. Having demonstrated the utility of such an approach, we then extended the application to the amino acid side chains. The calculation of the interaction of Kq with Ž . serine, cysteine, methionine, lysine, arginine, aspartate, histidine uncharged , tyrosine, tryptophan, and phenylalanine, both completes the parameterization of the molecular environments contained in the amino acids, and allows specific comment on these ion]functional group interactions. The cation]p interactions were of particular interest, given recent proposals in the literature and the fear that force fields would not be able to treat such interactions. We present a Ž w x . comprehensive comparison of the ab initio DFT BLYP , 6-311 G** and force Ž . field CHARMm22.0 assessments of these interactions. Q 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1515]1525, 1998
Hemorrhage from gastroesophageal lacerations following closed-chest cardiac massage.

Five cases of acute hemorrhage of the upper-gastro-intestinal tract due to gastric and esophageal lacerations complicating closed-chest cardiac massage were observed by an autopsy service of a general teaching hospital over a 16-month period. During the same time, 348 autopsies were performed, including 50 patients who had received closed-chest cardiac massage. Fractured ribs were found in 20 patients (40%) while gastric and esophageal lacerations were the second most frequently encountered significant complication (10%). Prevention, early recognition, and prompt decompression of acute gastric distention during cardiopulmonary resuscitation is emphasized as a method of preventing gastroesophageal lacerations during external cardiac massage.
HEMORRHAGIC STROKE IN THE STROKE PREVENTION BY AGGRESSIVE REDUCTION IN CHOLESTEROL LEVELS STUDY

Background: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having hemorrhagic stroke (n = 55 for active treatment vs n = 33 for placebo). Methods: We explored the relationships between hemorrhage risk and treatment, baseline patient characteristics, most recent blood pressure, and most recent low-density lipoprotein (LDL) cholesterol levels prior to the hemorrhage. Results: Of 4,731 patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p = 0.02), Cox multivariable regression including baseline variables significant in univariable analyses showed that hemorrhagic stroke risk was higher in those having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p p = 0.01), and with age (10y increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical interactions between these factors and treatment. Multivariable analyses also found that having Stage 2 (JNC-7) hypertension at the last study visit before a hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but there was no effect of most recent LDL-cholesterol level in those treated with atorvastatin. Conclusions: Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately affect the hemorrhagic stroke risk associated with these other factors. There were no relationships between hemorrhage risk and baseline low-density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in treated patients.
Production of D-Arabitol by Metschnikowia reukaufii AJ14787

A potent producer of D-arabitol was isolated by screening of natural sources and identified as Metschnikowia reukaufii AJ14787. Resting cells of this strain can efficiently produce D-arabitol from D-glucose with a weight yield of more than 60%, and can also produce D-arabitol from several other types of sugars such as polyols, ketoses, and aldoses. To improve productivity, various culture conditions such as temperature and the concentrations of D-glucose and nitrogen sources were examined. Under optimal conditions, 206 g/l of D-arabitol was produced from D-glucose with a weight yield of 52% in 100 hours.