Miracle-dz/UniFAR-FTUs huggingface dataset:
The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy

(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery.
PERILAKU BERISIKO DAN PERMASALAHAN KESEHATAN REPRODUKSI PADA REMAJA

Latar belakang . Penelitian ini untuk mengetahui gambaran umum tentang perilaku remaja terkait dengan kesehatan reproduksi dan permasalahannya di Kota Makassar tahun 2009. Metode . Lokasi penelitian dilakukan di Kota Makassar, dengan sampel dipilih secara purposive oleh petugas puskesmas setempat yaitu remaja laki-laki dan perempuan berusia antara 10-24 tahun yang memiliki masalah kesehatan, sudah menikah atau pun belum menikah yang berada di wilayah kerja 4 puskesmas terpilih. Penelitian menggunakan pendekatan kualitatif dalam pengumpulan data, yaitu dengan diskusi kelompok terarah ( F ocus G roup D iscussion ) dan wawancara mendalam ( indepth interview ) terhadap 30 remaja yang terpilih menjadi sampel. Hasil . Ditemukan bahwa remaja menikah di usia muda disebabkan karena hamil sebelum menikah, sudah tidak bersekolah dan adanya adat istiadat dan budaya salah satu suku yang menjodohkan dalam satu suku tersebut untuk mempertahankan harta kekayaan keturunan. Sebagian remaja menganggap perilaku seksual pranikah adalah biasa walaupun di sisi yang lain mereka mengakui bahwa hal tersebut adalah tidak benar, berdosa atau dilarang agama. Sebagian besar remaja mengetahui cara menghindari kehamilan yaitu dengan menggunakan alat kontrasepsi dan mengakhiri kehamilan dengan cara tradisional. Banyak remaja pria mengaku sudah biasa melakukan hubungan seksual dengan beberapa orang dengan alasan untuk mencari kesenangan. Perilaku menonton video atau melihat situs khusus dewasa melalui internet sudah dianggap biasa oleh remaja. Kesimpulan . Masih rendahnya pengetahuan remaja tentang kesehatan reproduksi termasuk penyakit menular seksual. Sebaliknya mereka mengetahui tentang penggunaan alat kontrasepsi dan cara-cara pengguguran kehamilan secara tradisional. Dalam berpacaran remaja mengaku biasa melakukan kontak fisik langsung seperti berpegangan tangan, berpelukan, berciuman dan aktivitas yang dapat mendorong kepada tindakan yang lebih jauh, seperti hubungan seksual. Penyuluhan dan konseling tentang kesehatan reproduksi sangat penting untuk mengurangi masalah pada remaja. Keywords : perilaku berisiko, kesehatan reproduksi, remaja
The FAP motif within human ATG7, an autophagy-related E1-like enzyme, is essential for the E2-substrate reaction of LC3 lipidation

ATG7 is an autophagy-related E1-like enzyme that is essential for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation. The existence of functional sequences at the amino-terminal region of human ATG7 remains uncertain. Mutational analyses of ATG7 revealed that both mutant ATG7ΔFAP lacking the FAP motif and ATG7FAPtoDDD, in which the Phe15-Ala16-Pro17 sequence was changed to Asp-Asp-Asp, could not complement defects in endogenous ATG12-conjugation and LC3-lipidation when expressed in Atg7-deficient mouse embryonic fibroblasts (MEFs). However, wild-type ATG7 complemented the defects in these cells. Overexpression of GFP-ATG10 and GFP-ATG12 rescued a defect in ATG12-conjugation in Atg7-deficient MEFs expressing mutant ATG7ΔFAP and ATG7FAPtoDDD, whereas overexpression of all ATG proteins related to ATG12-conjugation and LC3-lipidation could not rescue a defect in LC3-lipidation in Atg7-deficient MEFs expressing these ATG7 mutants. Both ATG7ΔFAP and ATG7FAPtoDDD mutants showed severe defects in the formation of an E2-substrate intermediate of ATG3 with LC3 in LC3-lipidation, but were able to form an E1-substrate intermediate of ATG7 with LC3 and the E1- and E2-substrate intermediates in ATG12-conjugation with reduced efficiency. These ATG7 mutants could also form the ATG12-ATG3 conjugate. Co-immunoprecipitation experiments revealed that the FAP motif of ATG7 is essential for the interaction of ATG7 with ATG3, but not for ATG7-homodimerization. These results indicated that the FAP motif of ATG7 is indispensable for formation of the ATG3-LC3 E2-substrate intermediate through the interaction of ATG7 with ATG3.
The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

In pancreatic β-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the β-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated β-cell death and focus on the role of autophagy in ameliorating ER stress. The development of drugs to take advantage of the potential protective effect of autophagy in ER stress, such as glucagon like peptide-1, will be a promising avenue of investigation.
It cuts both ways: an analysis of the psychological discourse on self-injury from a linguistic point of view.

This article proposes an analysis of the phenomenon of self-injury through the prism of current linguistic theories. The author uses the clinical distinctions made by Roman Jakobson between metonymic and metaphoric aphasia to suggest that the psychological community and those who harm themselves are participating in separate "language games. " While the clinical "language game" is characterized by the dominance of metaphor and a conception stressing the hierarchy between metaphor and metonymy, the "language game" of self-mutilators is dominated by metonymy. The author explores the clinical implications of understanding the language game of those who injure themselves as metonymic.
The airways pharmacology of DNK333, a potent, selective, non‐peptide dual NK1/NK2 receptor antagonist

The airways' pharmacology of DNK333 ((1R,3R,2E)‐N‐[3,4‐dichlorobenzyl)]‐4‐[(hexahydro‐2‐oxo‐1H‐azepin‐3‐yl)amino]‐N‐methyl‐3,5bis(trifluoromethyl) benzamide), a potent and selective dual NK1/NK2 neurokinin receptor antagonist is described in the present paper. DNK333 bound with high and similar affinities to human NK1 and NK2 receptors. In guinea‐pig isolated trachea, DNK333 induced concentration‐dependent blockade of the contractile responses to NK1‐ or NK2‐receptor agonists. In anaesthetized guinea‐pigs, DNK333 shifted the bronchoconstrictor dose‐response curves induced by NK1‐ and NK2‐receptor agonists by 21.8‐ (3 mg/kg) and 6.8‐fold (10 mg/kg), respectively. At 10 mg/kg, a 12‐h duration of action was observed. Nasal perfusion of substance P and capsaicin to anaesthetized guinea‐pigs induced extravasation, which was inhibited dose‐dependently by DNK333 (ED50 values 72 and 70 µg/kg, respectively). Exposure of conscious guinea‐pigs to 0.6 M citric acid resulted in cough and an increase in enhanced pause of respiratory function (Penh). Oral administration of DNK333 (0.3, 3, or 10 mg/kg, −2 h) inhibited cough by 62, 63, and 82%, respectively and the increase in Penh by 85.5 and 77.2% (3 and 10 mg/kg, respectively). Bronchoconstrictor responses in anaesthetized guinea‐pigs to intravenous injections of methacholine and substance P were increased 60 min after LPS challenge (1 mg/kg, i.v.). DNK333 (1 and 10 mg/kg) dosed intraduodenally 30 min prior to LPS challenge inhibited airway hyperreactivity in a dose‐dependent manner. In conclusion, DNK333 is a potent, orally bioavailable, dual NK1/NK2 receptor antagonist with a long duration of action. It inhibits bronchoconstriction, extravasation, cough, and airway hyperreactivity induced by endogenous release of neuropeptides, which renders DNK333 suitable for exploring the role of tachykinins in respiratory disease. Drug Dev Res 63:161–173, 2004. © 2004 Wiley‐Liss, Inc.
The vacuole within

The notochord is an evolutionarily conserved structure that has long been known to play an important role in patterning during embryogenesis. Structurally, the notochord is composed of two cell layers: an outer epithelial-like sheath, and an inner core of cells that contain large fluid-filled vacuoles. We have recently shown these notochord vacuoles are lysosome-related organelles that form through Rab32a and vacuolar-type proton-ATPase-dependent acidification. Disruption of notochord vacuoles results in a shortened embryo along the anterior-posterior axis. Interestingly, we discovered that notochord vacuoles are also essential for proper spine morphogenesis and that vacuole defects lead to scoliosis of the spine. Here we discuss the cellular organization of the notochord and how key features of its architecture allow the notochord to function in embryonic axis elongation and spine formation.
Ethnic/Racial Diversity and Posttraumatic Distress in the Acute Care Medical Setting

Recent commentary has advocated for epidemiological investigation as a foundational science for understanding disparities in the delivery of mental health care and for the development of early trauma–focused interventions. Few acute care investigations have examined the diversity of ethnic/racial heritages or compared variations in early posttraumatic distress in representative samples of injured trauma survivors. Hospitalized injury survivors at two United States level I trauma centers were randomly approached in order to document linguistic and ethnic/racial diversity. Approximately 12% of patients approached were non–English speaking with 16 languages represented. English speaking, inpatients were screened for posttraumatic stress disorder, peritraumatic dissociative, and depressive symptoms. For 269 English speaking study participants, ethnic/racial group status was clearly categorized into one group for 72%, two groups for 25%, and three groups for 3% of participants. Regression analyses that adjusted for relevant clinical and demographic characteristics revealed that relative to whites, patients from American Indian, African American, Hispanic, and Asian heritages demonstrated significant elevations in one or more posttraumatic symptom clusters. A remarkable diversity of heritages was identified, and posttraumatic distress was elevated in ethnic/racial minority patients. Policy–relevant clinical investigations that combine evidence–based treatments, bilingual/bicultural care–management strategies, and support for trauma center organizational capacity building may be required in order to enhance the quality of mental health care for diverse injured trauma survivors.
Does Psychoeducation Help Prevent Post Traumatic Psychological Distress?

Psychoeducation is increasingly used following trauma. The term covers the provision of information about the nature of stress, posttraumatic and other symptoms, and what to do about them. The provision of psychoeducation can also occur before possible exposure to stressful situations or, alternatively, after exposure. The intention of both is to ameliorate or mitigate the effects of exposure to extreme situations. Educational information can be imparted in a number of ways and can also form part of what has been termed psychological first aid. Despite its ubiquity, however, good evidence as to the value of psychoeducation is rare. Perhaps it could be assumed that psychoeducation, like education in general, is so obviously a “good thing” that it requires no evidence. In this paper we question the assumption, arguing that like any other intervention, psychoeducation needs to be backed up by empirical evidence. We will first present the case for and then the case against psychoeducation before reaching some conclusions and making some recommendations.
Staying Connected: A Feasibility Study Linking American Indian and Alaska Native Trauma Survivors to their Tribal Communities

The objective of this investigation was to assess the feasibility of a culturally tailored care management intervention for physically injured American Indian/Alaska Native (AI/AN) patients. The intervention was initiated at a Level I trauma center and aimed to link AI/AN patients to their distant tribal communities. Thirty AI/AN patients were randomized to the intervention or to usual care. Assessments at baseline, 3 months, and 6 months included self-reported lifetime cumulative trauma burden, Native healing requests, and symptoms of posttraumatic stress, depression, and alcohol use. Generalized estimating equations ascertained differences between groups over time. Ninety-four percent of eligible patients participated; follow-up at 3 and 6 months was 83%. Participants had high numbers of lifetime traumas (mean = 5.1, standard deviation = 2.6). No differences between the intervention and control groups were observed in posttraumatic stress symptoms, depression symptoms, or alcohol use at baseline or follow-up time points. Among intervention patients, 60% either requested or participated in traditional Native healing practices and 75% reported that the intervention was helpful. This effectiveness trial demonstrated the feasibility of recruiting and randomizing injured AI/AN patients. Future efforts could integrate evidence-based interventions and traditional Native healing into stepped collaborative care treatment programs.
Selection of rituximab dosage in chronic lymphocytic leukemia: where is the evidence?

Abstract Rituximab prolongs survival in many CD20-expressing B- lymphoid malignancies. In non-Hodgkin lymphoma (NHL), a large number of clinical studies have established the 375 mg/m2 dose of rituximab as standard. In chronic lymphocytic leukemia (CLL), response rates to single-agent rituximab at the NHL dose were low, but the use of higher doses or more frequent dosing have led to improved response rates, suggesting that a higher dose may be required. This led to the empiric decision to adopt rituximab at 500 mg/m2 in combination with fludarabine and cyclophosphamide (FC) in phase II and III trials in CLL. The final result was the approval of rituximab at 500 mg/m2 for treatment of CLL, in combination with FC. There is, however, preclinical evidence that full saturation of CD20 molecules may not be required to achieve chemosensitization in cancer cells, and it remains possible that the approved dose of 500 mg/m2 is higher than what is required to achieve maximal in vivo synergy. Nevertheless, all of the randomized evidence for superiority of rituximab plus chemotherapy over chemotherapy alone comes from studies using the 500 mg/m2 dose.
Magnetic force microscopy

Magnetic force microscopy (MFM) is an atomic force microscopy (AFM) based technique in which an AFM tip with a magnetic coating is used to probe local magnetic fields with the typical AFM spatial resolution, thus allowing one to acquire images reflecting the local magnetic properties of the samples at the nanoscale. Being a well established tool for the characterization of magnetic recording media, superconductors and magnetic nanomaterials, MFM is finding constantly increasing application in the study of magnetic properties of materials and systems of biological and biomedical interest. After reviewing these latter applications, three case studies are presented in which MFM is used to characterize: (i) magnetoferritin synthesized using apoferritin as molecular reactor; (ii) magnetic nanoparticles loaded niosomes to be used as nanocarriers for drug delivery; (iii) leukemic cells labeled using folic acid-coated core-shell superparamagnetic nanoparticles in order to exploit the presence of folate receptors on the cell membrane surface. In these examples, MFM data are quantitatively analyzed evidencing the limits of the simple analytical models currently used. Provided that suitable models are used to simulate the MFM response, MFM can be used to evaluate the magnetic momentum of the core of magnetoferritin, the iron entrapment efficiency in single vesicles, or the uptake of magnetic nanoparticles into cells.
Assessing the social validity of behavioral interventions: A review of treatment acceptability measures

Increased attention to the construct of social validity in school psychology research and practice has resulted in a focus on treatment acceptability, the extent to which interventions are considered appropriate, effective, and fair. Questionnaires represent the typical measurement approach to treatment acceptability. This article reviews treatment acceptability measures and practices that have been developed and used to assess the social validity of behavioral interventions. A comparative framework was developed and applied to provide a systematic critique of nine treatment acceptability measures along such dimensions as content and purpose of the instrument, psychometric properties, scoring procedures and interpretation, and use of the measure in research and practice. No one instrument was selected to be the most comprehensive and it is argued that treatment acceptability assessment practices need to move beyond the traditional questionnaire format. Alternatives to rating scales are presented and directions for future research regarding the measurement of treatment acceptability are discussed.
Assessment of Plasma Levels of Fasting Blood Glucose, Triglycerides, Total Cholesterol, and HbA1c in patients with Type 2 Diabetes Mellitus. -

Objective and Study Design: This was a cross-sectional study aimed to evaluate the significance of glycosylated Haemoglobin, triglycerides and total cholesterol in type 2 Saudi diabetic patients. Material and Methods: This study was conducted at Al- Quwayiyah City during the period between September 2012 and February 2013. The participants were 100 patients with type 2 diabetes and 50 apparently healthy individuals as control group. Venous blood samples were collected from all participants. The whole blood and sera were analyzed for glycosylated hemoglobin, fasting blood glucose and lipid profile. The statistical analysis was done by SPSS statistical package. Results: Plasma glucose, triglycerides and total cholesterol were significantly increased in diabetic patients compared with control group (P- value 0.000, 0.042 and 0.05 respectively). HbA1c showed positive correlations with fasting blood glucose, triglycerides and total Cholesterol (r = 0.554, P = 0.000, r = 0.288, P = 0.026 and r = 0. 283, P = 0.028 respectively). Conclusion: It is concluded from the results of this study that HbA1c can be used as a predictor of dyslipidemia in patients with type II diabetes.
Advances in the biology and therapy of chronic myeloid leukemia: proceedings from the 6th Post-ASH International Chronic Myeloid Leukemia and Myeloproliferative Neoplasms Workshop

Abstract Following the 53rd annual meeting of the American Society of Hematology (ASH) in San Diego in December 2011, a group of clinical and laboratory investigators convened for the 6th Post-ASH International Workshop on Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN). The Workshop took place on 13–14 December at the Estancia, La Jolla, California, USA. This report summarizes the most recent advances in the biology and therapy of CML that were presented at the ASH meeting and discussed at the Workshop. Preclinical studies focused on the CML stem cell and its niche, and on early results of deep sequencing of CML genomes. Clinical advances include updates on second- and third-generation tyrosine kinase inhibitors (TKIs), molecular monitoring, TKI discontinuation studies and new therapeutic agents. A report summarizing the pertinent advances in MPN has been published separately.
Effects of age on the prevalence of cardiac dysrhythmias in ponies

Summary This study describes the prevalence of cardiac dysrhythmias occurring over a single 24 h period in ponies and compares the heart rate and frequency of dysrhythmias in two groups of ponies of different ages. Electrocardiograms were recorded using a Holter monitoring system from twenty four ponies aged less than 15-year-old (n = 14) and greater than 15-year-old (n = 10). Subsequent analyses of cardiac rhythm revealed that only 3/24 ponies maintained a regular rhythm throughout the recording period. In the remaining 21 ponies, 6 different types of dysrhythmias were detected, the majority of which were vagally mediated; sinus arrhythmia (n = 12), sinoatrial block (n = 6) and second degree atrioventricular block (n = 10). Premature beats of both atrial (n = 3) and ventricular (n = 1) origin were observed only in the older group. There were no significant differences between the 2 groups with respect to mean 24-h heart rates or the prevalence of cardiac dysrhythmias.
Effect of G6PD Status in Malaria Infected Individuals on Haematological Parameters

The aim of this study was to determine the effect of G6PD status no haematological parameters in Plasmodium falciparum malaria infected and non-malaria infected individuals. The study was conducted at Federal Teaching Hospital, Ido-Ekiti, Nigeria. Malaria infected adult individuals; presented with signs and symptoms of malaria infection was used for the study. Two hundred and two blood samples were collected twice from the same malaria infected individuals; grouped as pre-treatment and post anti-malaria drug treatment. One hundred and two blood samples from apparently healthy individuals were collected for control; 5 ml of blood sample was collected and dispensed into di-potassium ethylenediaminetetracetic acid (K2EDTA) vaccutainer bottles for haemoglobin concentration, packed cell volume and red cell indices were analysed using haematology analyser, thick blood film was made and stained with Giemsa’s staining technique for malaria parasite detection, the procedure was described by Monica Cheesbrough. Glucose-6-Phosphate dehydrogenase (G-6-PD) was performed using methaemoglobin reduction method within 6 hours of sample collection. The procedure was as described by Dacie and Lewis. Data obtained was analysed using SPSS version 16. The result of this present study showed that, the mean±SD of Hb, PCV, MCV and MCH were significantly (P<0.05) lower in G6PD normal compared to G6PD deficient in pre and post anti-malaria drug treatment while mean±SD of RBC, Hb and PCV were significantly (P<0.05) higher in G6PD normal compared to G6PD deficient in control subjects. This present study showed that malaria attack in G6PD normal was observed more intensive compared to G6PD deficient.