Miracle-dz/UniFAR-FTUs huggingface dataset:
Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders.

OBJECTIVE The functional polymorphism in the promoter region of the SLC6A4/5-HTT serotonin transporter gene (5-HTTLPR) has been linked to altered stress response. Carriers of the short (s-) allele have increased negative psychological reactions and stress hormone release compared with carriers of the long (l-) allele, interacting with severe life events including childhood trauma. High stress levels are associated with cognitive impairments in a variety of clinical and experimental studies. Patients with psychotic disorders are characterized both by more childhood traumatic events and abnormal stress responses and by significant but highly variable cognitive dysfunction. We hypothesize that 5-HTTLPR variations and long-term effects of childhood trauma interact and contribute to some of the variation in cognitive dysfunction seen in patients with psychotic disorders. METHODS Patients with psychotic disorders (schizophrenia and affective spectrums) were recruited from a catchment area-based treatment organization. History of childhood abuse was obtained by the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive, standardized neuropsychological test battery. 5-HTTLPR genotypes were analyzed using standard polymerase chain reaction. RESULTS We observed a significant interaction between 5-HTTLPR variants and childhood trauma across cognitive domains; here, homozygotic s-carriers exposed to high levels of childhood trauma (physical neglect and abuse) had significantly poorer cognitive functioning than all other groups. CONCLUSIONS Our results need replication but underline the importance of investigating childhood trauma and its interaction with genetic markers when studying cognitive dysfunction in patients with psychotic disorders.
IMPLEMENTASI SISTEM INFORMASI ADMINISTRASI RUMAH SAKIT BERBASIS KUMPUTER UNTUK MENINGKATKAN KINERJA KARYAWAN (Studi pada Billing Systems RSUD Dr.Saiful Anwar Malang)

Rumah sakit umum Dr. Saiful Anwar Malang merupakan rumah sakit umum daerah kelas A yang telah terakreditasi penuh dan bersertifikat ISO 9001 : 2008. Sebagai rumah sakit umum daerah yang besar tentunya harus memiliki sistem informasi administrasi yang baik agar dapat melayani pengunjung dengan optimal. Penelitian ini membahas tentang bagaimana implementasi sistem informasi administrasi berbasis komputer yang telah diterapkan. Lalu apa saja kelebihan dan kekurangan sistem tersebut dan dampaknya untuk peningkatan kinerja karyawan. Penelitian ini menggunakan metode penelitian kualitatif. Hasil penelitian ini bahwa implementasi sistem informasi administrasi rumah sakit sudah diterapkan sejak tahun 1995 yaitu menggunakan Billing Systems. Terjadi peningkatan kinerja karyawan yaitu dapat menyelesaikan pekerjaan lebih cepat, meminimalisir kesalahan dan dapat menyelesaikan pekerjaan sesuai dengan waktu yang ditentukan. Kata Kunci : Sistem Informasi berbasis Komputer ABSTRACT General hospital Dr. Saiful Anwar Malang is a general hospital “A” class that has been fully accredited and certified ISO 9001: 2008. As public hospitals of the area would to have a good administrative information system in order to serve visitors to the optimum. This study discusses how the implementation of computer-based administrative information systems that have been implemented. So what are the advantages and disadvantages of these systems and their impact on employee performance improvement. This study used qualitative research methods. Results of this study that the implementation of a hospital information system administration has been applied since 1995, namely using Billing Systems. An increase in employee performance that can get the job done more quickly, minimize errors, and can complete the work in accordance with the specified time. Keywords: Information Systems
Noonan syndrome in diverse populations

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low‐set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
Anticoagulant Activity of a Unique Sulfated Pyranosic (1→3)-β-l-Arabinan through Direct Interaction with Thrombin*

Background: Many seaweed polysaccharides have anticoagulant activity, but the mechanism of action was elucidated in a few cases. Results: A highly sulfated pyranosic β-arabinan exerts its activity through direct and indirect inhibition of thrombin. Conclusion: The structure and mechanism of action of the arabinan are different from those found for other polysaccharides. Significance: This arabinan could be an alternative anticoagulant in certain specific cases. A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans.
The Archaeal Proteasome Is Regulated by a Network of AAA ATPases*

Background: The AAA ATPases of the PAN/Rpt1–6 group regulate access of substrates to the 20S proteasome. Results: Two groups of AAA proteins, CDC48 and AMA, function as novel proteasomal ATPases in archaea. Conclusion: This network of regulatory ATPases increases the capacity of proteasomal protein degradation in archaea. Significance: Diversification at the level of the regulatory ATPase provides a contrast to the fully differentiated 26S proteasome of eukaryotes. The proteasome is the central machinery for targeted protein degradation in archaea, Actinobacteria, and eukaryotes. In its basic form, it consists of a regulatory ATPase complex and a proteolytic core particle. The interaction between the two is governed by an HbYX motif (where Hb is a hydrophobic residue, Y is tyrosine, and X is any amino acid) at the C terminus of the ATPase subunits, which stimulates gate opening of the proteasomal α-subunits. In archaea, the proteasome-interacting motif is not only found in canonical proteasome-activating nucleotidases of the PAN/ARC/Rpt group, which are absent in major archaeal lineages, but also in proteins of the CDC48/p97/VAT and AMA groups, suggesting a regulatory network of proteasomal ATPases. Indeed, Thermoplasma acidophilum, which lacks PAN, encodes one CDC48 protein that interacts with the 20S proteasome and activates the degradation of model substrates. In contrast, Methanosarcina mazei contains seven AAA proteins, five of which, both PAN proteins, two out of three CDC48 proteins, and the AMA protein, function as proteasomal gatekeepers. The prevalent presence of multiple, distinct proteasomal ATPases in archaea thus results in a network of regulatory ATPases that may widen the substrate spectrum of proteasomal protein degradation.
The Influence of trisomy 21 on facial form and variability

Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live‐born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age‐matched (4–12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS‐sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype–phenotype map.
Bacteriophages for the treatment of Pseudomonas aeruginosa infections

Bacteriophages were first identified in 1915 and were used as antimicrobial agents from 1919 onwards. Despite apparent successes and widespread application, early users did not understand the nature of these agents and their efficacy remained controversial. As a result, they were replaced in the west by chemical antibiotics once these became available. However, bacteriophages remained a common therapeutic approach in parts of Eastern Europe where they are still in use. Increasing levels of antibiotic‐resistant bacterial infections are now driving demand for novel therapeutic approaches. In cases where antibiotic options are limited or nonexistent, the pressure for new agents is greatest. One of the most prominent areas of concern is multidrug‐resistant Gram‐negative bacteria. Pseudomonas aeruginosa is a prominent member of this class and is the cause of damaging infections that can be resistant to successful treatment with conventional antibiotics. At the same time, it exhibits a number of properties that make it a suitable target for bacteriophage‐based approaches, including growth in biofilms that can hydrolyse following phage infection. Pseudomonas aeruginosa provides a striking example of an infection where clinical need and the availability of a practical therapy coincide.
UBE2A deficiency in two siblings: A novel splicing variant inherited from a maternal germline mosaicism

UBE2A deficiency is a syndromic condition of X‐linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond‐shaped, and deep‐set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X‐linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X‐exome. The synonymous c.330G>A substitution in UBE2A modifies the last nucleotide of exon 5, causing the exon skipping and resulting in an out‐of‐frame transcript, likely encoding for a truncated form of the ubiquitin‐conjugating enzyme E2 A. As confirmed by deep sequencing, the c.330G>A substitution in UBE2A was undetectable in genomic DNA from maternal blood cells, suggesting that the recurrent UBE2A deficiency observed in males of this family is caused by a maternal germline mosaicism.
Sumoylation Is Important for Stability, Subcellular Localization, and Transcriptional Activity of SALL4, an Essential Stem Cell Transcription Factor*

Background: SALL4 is a key stem cell transcription factor that transactivates OCT4. Results: SALL4B is modified by sumoylation. Conclusion: Sumoylation plays an important role in regulating SALL4B stability, subcellular localization, and transcriptional activities. Significance: Sumoylation functions a major post-translational mechanism for regulating stem cell transcription factors. SALL4 is a transcription factor that plays a key role in the maintenance and self-renewal of embryonic stem cells and hematopoietic stem cells. Given that little is known about regulation of SALL4, we studied biochemical modifications of SALL4B, a major splicing variant of SALL4, and elucidated their biological function. SALL4B was primarily modified by ubiquitination when it was expressed in both Sf9 and HEK293T cells. A significant fraction of SALL4B was further modified by sumoylation when it was expressed in HEK293T cells. Constitutive SUMO-modification of SALL4B was also detected in Tera-1, a cell line of the teratocarcinoma origin. SALL4B sumoylation was independent of ubiquitination and lysine residues 156, 316, 374, and 401 were essential for sumoylation. Chromatin fraction contained more SUMO-deficient SALL4B. Despite a shorter half-life than the wild-type counterpart, SUMO-deficient SALL4B interacted with OCT4 more efficiently than the wild-type SALL4B. RNAi-mediated silencing of SALL4 expression caused significant down-regulation of both OCT4 and SOX2, which was rescued by ectopic expression of SALL4B but not by SUMO-deficient mutant. Significantly, compared with the wild-type SALL4B, SUMO-deficient mutant exhibited compromised trans-activation or trans-repression activities in reporter gene assays. Combined, our studies reveal sumoylation as a novel form of post-translational modification for regulating the stability, subcellular localization, and transcriptional activity of SALL4.
Degradation of an Old Human Protein

Background: Long-lived proteins degrade over time. Results: Lens γS-crystallin is extensively modified with age, and truncation near the C terminus generates a peptide that binds tightly to cell membranes. Conclusion: The peptide released from γS-crystallin can adopt an α-helical conformation and may alter permeability by interacting with cell membranes. Significance: Peptide binding may explain why human lens membranes change with age. Long-lived proteins exist in a number of tissues in the human body; however, little is known about the reactions involved in their degradation over time. Lens proteins, which do not turn over, provide a useful system to examine such processes. Using a combination of Western blotting and proteomic methodology, age-related changes to a major protein, γS-crystallin, were studied. By teenage years, insoluble intact γS-crystallin was detected, indicative of protein denaturation. This was not the only change, however, because blots revealed evidence of significant cross-linking as well as cleavage of γS-crystallin in all adult lenses. Cleavage at a serine residue near the C terminus was a major reaction that caused the release of a 12-residue peptide, SPAVQSFRRIVE, which bound tightly to lens cell membranes. Several other crystallin-derived peptides with double basic residues also lodged in the cell membrane fraction. Model studies showed that once cleaved from γS-crystallin, SPAVQSFRRIVE adopts a markedly different shape from that in the intact protein. Further, the acquired helical conformation may explain why the peptide seems to affect water permeability. This observation may help explain the changes to cell membranes known to be associated with aging in human lenses. Age-related cleavage of long-lived proteins may therefore yield peptides with untoward biological activity.
Crystal Structures of the Scaffolding Protein LGN Reveal the General Mechanism by Which GoLoco Binding Motifs Inhibit the Release of GDP from Gαi *

Background: GoLoco (GL) motif binds to Gα and inhibits its guanine nucleotide dissociation. Results: Crystal structures of LGN-GL3(4)·Gαi1(3) complexes reveal a double Arg finger-mediated GDP recognition mechanism, which is distinct from that shown in the RGS14·Gαi1 complex. Conclusion: LGN-GL/Gαi interaction might represent a general binding mode between GoLoco motifs and Gαi. Significance: Our findings shed new light on the GoLoco motif-mediated G protein signaling regulation. GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Gα subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Gαi/o during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Gαi·GDP. The crystal structures of Gαi·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Gαi interaction features when compared with the only high resolution structure known with GL/Gαi interaction between RGS14 and Gαi1. Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Gαi·GDP. A highly conserved “double Arg finger” sequence (RΨ(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Gαi. Together with the sequence alignment, we suggest that the LGN GL/Gαi interaction represents a general binding mode between GL motifs and Gαi. We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors.
Association study between the TNXB locus and schizophrenia in a Japanese population

The chromosome 6p21–24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty‐six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia. © 2006 Wiley‐Liss, Inc.
Stabilization of a Prion Strain of Synthetic Origin Requires Multiple Serial Passages*

Background: Strain adaptation accompanies cross-species transmission of prions. Results: Adaptation of a strain of synthetic origin was observed within the same host species. Conclusion: When induced by recombinant PrP fibrils, PrPSc properties evolve over multiple serial passages within the same host. Significance: The phenomenon of prion strain adaptation is more common than generally thought. Transmission of prions to a new host is frequently accompanied by strain adaptation, a phenomenon that involves reduction of the incubation period, a change in neuropathological features and, sometimes, tissue tropism. Here we show that a strain of synthetic origin (SSLOW), although serially transmitted within the same species, displayed the key attributes of the strain adaptation process. At least four serial passages were required to stabilize the strain-specific SSLOW phenotype. The biological titration of SSLOW revealed a correlation between clinical signs and accumulation of PrPSc in brains of animals inoculated with high doses (10−1-10−5 diluted brain material), but dissociation between the two processes at low dose inocula (10−6-10−8 diluted brain material). At low doses, several asymptomatic animals harbored large amounts of PrPSc comparable with those seen in the brains of terminally ill animals, whereas one clinically ill animal had very little, if any, PrPSc. In summary, the current study illustrates that the phenomenon of prion strain adaptation is more common than generally thought and could be observed upon serial transmission without changing the host species. When PrPSc is seeded by recombinant PrP structures different from that of authentic PrPSc, PrPSc properties continued to evolve for as long as four serial passages.