Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of chemokines, MCP‐1, and KC in the mutant huntingtin expressing neuronal cells because of proteasomal dysfunction

Huntington’s disease is a hereditary neurodegenerative disorder caused by an aberrant polyglutamine expansion in the amino terminus of the huntingtin protein. The resultant mutant huntingtin form aggregates in neurons and causes neuronal dysfunction and degeneration in many ways including transcriptional dysregulation. Here, we report that the expression of mutant huntingtin in the mouse neuroblastoma cell results in massive transcriptional induction of several chemokines including monocyte chemoattractant protein‐1 (MCP‐1) and murine chemokine (KC). The mutant huntingtin expressing cells also exhibit proteasomal dysfunction and down‐regulation of NF‐κB activity in a time‐dependent manner and both these phenomena regulate the expression of MCP‐1 and KC. The expression of MCP‐1 and KC are increased in the mutant huntingtin expressing cells in response to mild proteasome inhibition. However, the expression of MCP‐1 and KC and proteasome activity are not altered and inflammation is rarely observed in the brain of 12‐week‐old Huntington’s disease transgenic mice in comparison with their age‐matched controls. Our result suggests that the mutant huntingtin‐induced proteasomal dysfunction can up‐regulate the expression of MCP‐1 and KC in the neuronal cells and therefore might trigger the inflammation process.
Aortic stenosis in infants.

THE clinical profile and results of operation in children and adults with congenital aortic stenosis have been reported from this department earlier.1 , 3 It is the purpose of this presentation to discuss patients with aortic stenosis first seen at Children's Hospital Medical Center, Boston, in infancy. Since the symptoms and signs of, as well as the prognosis of and operative approach to, these patients is significantly different from that noted in the older age group, it seemed logical to discuss these infants separately. Material and Methods The 24 patients forming the basis of this discussion represent all the infants with aortic .
Co-translational Interactions of Apoprotein B with the Ribosome and Translocon during Lipoprotein Assembly or Targeting to the Proteasome*

Hepatic lipoprotein assembly and secretion can be regulated by proteasomal degradation of newly synthesized apoB, especially if lipid synthesis or lipid transfer is low. Our previous studies in HepG2 cells showed that, under these conditions, newly synthesized apoB remains stably associated with the endoplasmic reticulum (ER) membrane (Mitchell, D. M., Zhou, M., Pariyarath, R., Wang, H., Aitchison, J. D., Ginsberg, H. N., and Fisher, E. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 14733–14738). We now show that independent of lipid synthesis, apoB chains that appear full-length are, in fact, incompletely translated polypeptides still engaged by the ribosome and associated with the ER translocon. In the presence of active lipid synthesis and transfer, translation and lipoprotein assembly are completed, and the complexes exit the ER. Upon omitting fatty acids from, or adding a microsomal triglyceride transfer protein inhibitor to, culture media to reduce lipid synthesis or transfer, respectively, apoB was degraded while it remained associated with the ER and complexed with cytosolic hsp70 and proteasomes. Thus, unlike other ER substrates of the proteasome, such as major histocompatibility complex class I molecules, apoB does not fully retrotranslocate to the cytosol before entering the ubiquitin-proteasome pathway. Although, upon immunofluorescence, apoB in proteasome-inhibited cells accumulated in punctate structures similar in appearance to aggresomes (cytosolic structures containing molecules irreversibly lost from the secretory pathway), these apoB molecules could be secreted when lipid synthesis was stimulated. The results suggest a model in which 1) apoB translation does not complete until lipoprotein assembly terminates, and 2) assembly with lipids or entry into the ubiquitin-proteasome pathway occurs while apoB polypeptides remain associated with the translocon and attached to the ribosome.
Proteomic analysis of the excretory‐secretory proteins of the Trichinella spiralis L1 larva, a nematode parasite of skeletal muscle

Trichinella spiralis is an intracellular nematode parasite of mammalian skeletal muscle. Infection of the muscle cell leads to the formation of a host‐parasite complex that results in profound alterations to the host cell and a re‐alignment of muscle‐specific gene expression. The role of parasite excretory‐secretory (ES) proteins in mediating these effects is currently unknown, largely due to the difficulty in identifying and assigning function to individual proteins. In this study, a global proteomics approach was used to analyse the ES proteins from T. spiralis muscle larvae. Following 2‐DE of ES proteins,MALDI‐TOF‐MS and LC‐MS/MS were used to identify the peptide spots. Specific Trichinella EST databases were assembled and used to analyse the data. Despite the current absence of a Trichinella genome‐sequencing project, 43 out of 52 protein spots analysed were identified and included the major secreted glycoproteins. Other novel proteins were identified from matches with sequences in the T. spiralis database. Our results demonstrate the value of proteomics as a tool for the identification of Trichinella ES proteins and in the study of the molecular mechanism underpinning the formation of the host‐parasite complex during Trichinella infections.
An evolutionary Bayesian belief network methodology for participatory decision making under uncertainty: An application to groundwater management

An integrated participatory approach based on Bayesian belief network (BBN) and evolutionary multiobjective optimization is proposed as an efficient decision‐making tool in complex management problems. The proposed methodology incorporates all the available evidence and conflicting objectives to evaluate implications of alternative actions in the decision‐making process and suggests best decision pathways under uncertainty. A BBN provides a framework within which the contributions of stakeholders can be taken into account. It allows a range of different factors and their probabilistic relationship to be considered simultaneously. It takes into account uncertainty by assigning probability to those variables whose states are not certain. The integration of BBN with evolutionary multiobjective optimization allows the analysis of tradeoff between different objectives and incorporation and acknowledgement of a broader set of decision goals into the search and decision‐making process. The proposed methodology can be used as a decision support tool to model decision‐making processes for complex problems. It deals with uncertainties in decision making pertaining to human behavior and checks for consistency of the developed BBN structure and the parameters of the probabilistic relationship by uncovering discrepancies in the decision analysis process (e.g., bias in completeness or redundancy of the model based on a utility function). It generates a set of efficient management options (appropriate combinations of interventions) that balances conflicting objectives. The effectiveness of the proposed methodology is discussed through application to a real case study. It is shown that it successfully identifies any inconsistencies in the developed BBN models and generates large numbers of management options that achieve an optimal tradeoff between different objectives. Integr Environ Assess Manag 2012; 8: 456–461. © SETAC
A review of locomotion mechanisms of urban search and rescue robot

– This study aims to investigate locomotion mechanisms of different urban search and rescue (USAR) robots currently being researched or commercially available on the market. , – USAR robots are categorized by the type of their mobility. Detailed illustration and analysis have been given for each USAR robot in the paper. , – The paper finds that none of current USAR robots can practically and autonomously carry out rescue work in a complex and unstructured environment. Hence, responding to the practical requirements of highly challenging USAR tasks, a team of USAR robots based on different locomotion mechanisms may be a good solution to undertake rescue activities. , – The paper provides guidance in the design of future USAR robots. , – The paper investigates locomotion mechanisms of different USAR robots in detail.
Further evidence for the role of IP3R1 in regulating subsynaptic gene expression and neuromuscular transmission

The inositol 1,4,5-triphosphate IP3R channel is highly expressed on specialized ER membrane, where it initiates a slow wave of Ca2+ release from internal stores, allowing subcellular compartmentalization of Ca2+ signals. In skeletal muscle, IP3R1 is also highly concentrated at some myonuclei, particularly near the NMJ. We have reported that in fully developed adult muscle, IP3R1 knockdown by siRNA increases synaptic strength at both pre- and post-synaptic sites of neuromuscular transmission, increasing both the amplitude and frequency of spontaneous quantal events and quantal content, as well as expression of AChR subunits and other NMJ-specific genes. Here, we demonstrate that reducing IP3R1 activity in mouse TA muscle by promoting hydrolysis locally of IP3R1 also amplifies expression of subsynaptic genes and transcription factors. Furthermore, using a retrograde tracer, cholera toxin B subunit, we find that siRNA-mediated silencing of IP3R1 in TA muscle increases vesicle trafficking. These studies suggest that postsynaptic IP3R1 activity regulates synaptic gene expression and neuromuscular transmission.
Effect of arsenic trioxide on inhibition of restenosis after rabbit vascular injury and its mechanism.

OBJECTIVE To investigate the effect and mechanism of arsenic trioxide (As(2)O(3)) on the prevention of restenosis after vascular injury. METHODS Apoptosis induction of As(2)O(3) on cultured rabbit vascular smooth muscle cells (VSMCs) in vitro was observed. Thirty-two New Zealand white rabbits were randomly divided into 2- and 4-wk study groups, and their controls. 10% As(2)O(3) at 2.5 mg x Kg(-1) x d(-1) or 0.9% sodium chloride was intraperitoneally infused for 3 days before left common carotid arteries were denudated with a balloon. After denudation 2- and 4-wk animals were sacrificed for morphometry and immunohistochemical studies on carotid arteries, and for histopathology on liver and kidney. RESULTS It was shown via cellular morphology and DNA fragments in electrophoresis that promotion of As(2)O(3) on cultured vascular smooth muscle cell apoptosis was dependent upon its concentration and duration. Compared with the control animals, the mean vascular intimal proliferation areas were reduced in 2-wk study animals (P < 0.05) and no difference was shown in 4-wk (P > 0.05), while the mean vascular luminal areas were all enlarged in both study groups (all P < 0.05). The downregulated bcl-2 expression (all P < 0.05 in 2- and 4-wk) and the upregulated bax expression (P < 0.01 in 2-wk; P < 0.05 in 4-wk) were detected by immunohistochemistry, in comparison with control groups. Gene bcl-2 and bax protein expression were consistent with the suppression of intimal proliferation and the enlargement of luminal areas in corresponding sections. CONCLUSION As(2)O(3) induces apoptosis of VSMCs and inhibits experimental restenosis effectively after artery injury, via downregulation of bcl-2 and upregulation of bax expression.
Knowledge and risk perception of measles and factors associated with vaccination decisions in subjects consulting university affiliated public hospitals in Lyon, France, after measles infection

In 2011, a large number of European countries faced measles outbreaks, France accounting for more than half of the reported cases. The Rhône-Alpes region, located in south-east France, was one of the most affected provinces, with an incidence rate of 97.9 cases per 100 000 inhabitants. We conducted a retrospective survey of adults and parents of children consulting university affiliated public hospitals because of measles infections between January 1, 2010 and September 2012 in Lyon, France. Our main objectives were to evaluate (1) the level of study population knowledge of measles, (2) vaccination practices, and (3) changes in opinion with regard to measles vaccination after disease onset. Overall, 73.64% of patients were not vaccinated or partially vaccinated. The main reason for non-vaccination in children was inappropriate age while among non-vaccinated adults, 29.3% could not give any reason. In total, 29.1% of the responding parents and 24.2% of adult cases were opposed to vaccination “in principle. ” A large number of patients did not recognize measles as a serious illness and were unaware of its complications. Among parents of infected children, knowledge of transmission mode (odds ratio [OR] = 5.9; 95% confidence interval [95% CI]: 1.64–21.26), perceived severity of measles (OR = 1.5; 95% CI: 1.06–2.13), and absence of hepatitis B vaccination (OR = 0.17; 95% CI: 0.04–0.65) were independently associated with a more positive opinion about measles vaccination after disease onset. In adult patients, low education level (OR = 3.39; 95% CI: 1.03–11.11) and lack of knowledge of sequelae (OR = 10.19; 95% CI: 1.14–91.31) were linked with a more positive opinion. Individuals affected by vaccine-preventable diseases are interesting populations to study disease impact on vaccine perception.
C‐reactive protein in patients undergoing cardiac surgery

Among 25 patients undergoing cardiac surgery with the aid of cardiopulmonary bypass, 13 who recovered uneventfully all had normal (< 2 mg/litre) levels of serum C‐reactive protein pre‐operatively. In contrast, 10 of the 12 patients who suffered from various postoperative complications, including two who died, had abnormally raised levels of C‐reactive protein pre‐operatively. AN patients showed a major acute phase response to surgery with peak C‐reactive protein levels at about 46 hours but, whereas the uncomplicated cases showed a characteristic smooth biphasic pattern of declining levels thereafter, the complicated cases all exhibited significant alterations of this pattern. The occurrence during the postoperative period of a secondary rise in C‐reactive protein or the failure of the level to continue falling, generally preceded clinical evidence of intercurrent infection. Pre‐operative measurement of serum C‐reactive protein may thus make a valuable contribution to the assessment of patients requiring elective cardiac surgery; regular postoperative monitoring can provide early warning of serious complications.
Acute Re-Feeding Reverses Food Restriction-Induced Hypothalamic-Pituitary-Gonadal Axis Deficits1

Abstract Undernutrition has well-established effects on female reproduction. Here we describe the effects of food restriction on aspects of the hypothalamic-pituitary-gonadal (HPG) axis in the female musk shrew. We determined that acute re-feeding reverses deficits brought on by food restriction. Two days of food restriction led to an increase in proGnRH immunoreactive cells in the preoptic area relative to ad libitum-fed controls (AL). This increase was reversed by 90 min of ad libitum feeding in the re-fed females (RF). In addition, food-restricted (FR) females had significantly greater GnRH content in the median eminence than either the AL or RF females. After GnRH was administered, the majority of females in all food conditions ovulated, yet the FR females had significantly fewer corpora lutea than either the AL or RF animals. These data show that food restriction impairs HPG axis function in female musk shrews, and that some of these impairments can be rapidly reversed by acute re-feeding.
Prevalence of anxiety and depression among medical students of private university.

OBJECTIVE To assess anxiety and depression levels among medical students of a private university by using a self-administered anxiety and depression questionnaire. METHODOLOGY A cross sectional study was done on the students of Ziauddin Medical University, who had spent more than six months in the medical school. A self-administered questionnaire was given to the students, present in the class and willing to participate in the study. During the survey students of 5th year were not available. The instrument used to asses the anxiety and depression levels was the, Aga Khan University Anxiety and Depression Scale (AKUADS). Additional questions regarding socioeconomic variables were also included in the survey instrument, such as student's birth order, monthly income, number of siblings, and monthly expenditure on education. Data analysis was done on Epi info version 6. RESULTS There were 252 students in 4th year MBBS to 1st year MBBS. Of these 189 were present during the survey. Using anxiety and depression scale it was found out that 113 (60%) students had anxiety and depression. Prevalence of anxiety and depression in students of 4th year, 3rd year, 2nd year and 1st year was 49%, 47%, 73% and 66% respectively. It was significantly higher in 1st year and 2nd year, as compared to 3rd and 4th year (p < 0.05). It was seen that birth order, monthly income, number of siblings and monthly expenditure on education did not affect the prevalence of anxiety and depression. CONCLUSION This study suggests that medical students experience anxiety and depression, the finding is consistent with other western studies, however there is no local data available to support our findings. The study finding highlights the need of psychiatric counseling and support services available to vulnerable students. These findings should be further explored in longitudinal studies to identify the stressors leading to these outcomes and appropriate interventions.
Mammalian sperm acrosome: formation, contents, and function.

Sperm-egg interaction is a carbohydrate-mediated species-specific event which initiates a signal transduction cascade resulting in the exocytosis of sperm acrosomal contents (i.e., the acrosome reaction). This step is believed to be a prerequisite which enables the acrosome-reacted spermatozoa to penetrate the zona pellucida (ZP) and fertilize the egg. Successful fertilization in the mouse and several other species, including man, involves several sequential steps. These are (1) sperm capacitation in the female genital tract; (2) binding of capacitated spermatozoa to the egg's extracellular coat, the ZP; (3) induction of acrosome reaction (i.e., sperm activation); (4) penetration of the ZP; and (5) fusion of spermatozoon with the egg vitelline membrane. This minireview focuses on the most important aspects of the sperm acrosome, from its formation during sperm development in the testis (spermatogenesis) to its modification in the epididymis and function following sperm-egg interaction. Special emphasis has been given to spermatogenesis, a complex process involving multiple molecular events during mitotic cell division, meiosis, and the process of spermiogenesis. The last event is the final phase when a nondividing round spermatid is transformed into the complex structure of the spermatozoon containing a well-developed acrosome. Our intention is also to briefly discuss the functional significance of the contents of the sperm acrosome during fertilization. It is important to mention that only the carbohydrate-recognizing receptor molecules (glycohydrolases, glycosyltransferases, and/or lectin-like molecules) present on the surface of capacitated spermatozoa are capable of binding to their complementary glycan chains on the ZP. The species-specific binding event starts a calcium-dependent signal transduction pathway resulting in sperm activation. The hydrolytic and proteolytic enzymes released at the site of sperm-zona interaction along with the enhanced thrust of the hyperactivated beat pattern of the bound spermatozoon, are important factors in regulating the penetration of the zona-intact egg.
A cross-cultural comparison of pressures to switch left-hand writing: Brazil versus Canada

Attempts to switch left-hand preferences towards the right side are socialisation practices found in many countries (Perelle & Ehrman, 1994). Although researchers acknowledge that pressures against left-hand use contribute to the cross-cultural fluctuations in the prevalence of left- versus right-hand preference, there has been little systematic cross-cultural study of how these pressures are applied, and who are the major agents applying the pressures to change. Our study explored specific rightward conversion practices and the results of these practices among individuals from two countries. One sample of participants was from a culture categorised as formal, Brazil, and the second sample was from Canada, a nonformal culture (Hofstede, 2001). Researchers have argued that prevalence rates of right-handedness should be higher in cultures that value conformity, called formal cultures, and lower among members of nonformal cultures where conformity pressures are lax (Medland, Perelle, De Monte, & Ehrman, 2004). The socialisation practices used to foster a change from the left to the right side are also predicted to differ in frequency and in kind in formal versus nonformal cultural settings. These cultural differences are assumed to result in differences in success rates of the conversion attempts, with formal cultures producing higher numbers of successfully converted right-handers. Our findings indicate that the formal versus nonformal cultural explanation for cross-cultural fluctuations in the prevalence of hand preference types does not account for the characteristics of the rightward conversion experiences reported by participants in the two groups. We propose that hypotheses concerning the effects of cultural differences on hand preference formation be expanded to include possible biological or genetic variance between groups.
Secure Content Based Routing in Tactical Mobile Ad Hoc Networks

Information superiority in future network centric warfare requires bandwidth efficient data dissemination to the right person at the right time with high assurance. This paper presents a secure content based routing approach for information dissemination in tactical networks. In this approach, subscription is expressed in terms of information items. This approach is more general and flexible than dissemination based on multicast addresses, and avoids the problem of pre-deployment multicast address planning for dynamic engagement situations in battle fields. To be bandwidth efficient, the proposed approach establishes routing paths taking into account overlapping information needs of different nodes. Secure dissemination is founded on a novel concept that separates the concerns of key management for trusted communication (entitlement grouping) from that of disseminating only specific information items that are of interest to recipients (dissemination grouping). The proposed approach provides an integrated scheme that facilitates entitlement based key management for protecting contents in packet payloads and content markup in packet headers for content based routing. The content markup enables intermediate forwarding nodes to employ efficient bandwidth utilization techniques without examining packet contents, thus reducing security vulnerabilities