Sexually transmitted diseases among female commercial sex workers in Finote Selam town, northwest Ethiopia: a community-based cross-sectional study.
Female commercial sex workers (FCSWs) are considered a high-risk group for acquiring sexually transmitted diseases (STDs), yet the reported prevalence varies in studies around the world. The aim of this study was to determine the magnitude and associated factors of STDs among female sex workers. A community-based cross-sectional study was conducted among female sex workers in Finote Selam town. A total of 389 sex workers were studied using census method. Data were collected using an interview with structured questionnaires. The data were entered and analyzed by using SPSS version 20 software package. The findings of this study showed that the overall prevalence of STDs was 20.6%. The reported prevalence of genital discharge, ulcer, and bubo was 15.9%, 15.2%, and 11.6%, respectively. In the multivariable logistic regression analysis, respondents who did not use a condom were about four times at higher risk of STDs than those who were using a condom consistently (adjusted odds ratio [AOR] = 4.07; 95% confidence interval [CI]: 1.812, 9.139). Respondents who experienced condom breakages were more than 12 times more likely to report STDs than those who never experienced condom breakages (AOR = 12.291, 95% CI: 5.701, 26.495). The findings of this study showed that one in five commercial sex workers in Finote Selam town had STDs. Sex without a condom and condom breakage during sexual intercourse showed a significant association with STDs. Therefore, the Woreda Health Office in collaboration with nongovernmental organizations in the area should work on safe sex promotion to enhance consistent condom use and reduce condom breakage through continuous education among commercial sex workers.


Lactose and D-galactose catabolism in the filamentous fungus Aspergillus nidulans.
The disaccharide lactose is a byproduct of cheese production accumulating to amounts of 800,000 tons per year worldwide, of which 15% is used as a carbon source for various microbial fermentations. Nevertheless, little is known about the regulation of its metabolism in filamentous fungi. Lactose is metabolized slowly, and some important fungi such as A. niger cannot use it at all. A more detailed knowledge on the rate-limiting steps would be helpful to improve its industrial application. We have chosen A. nidulans as an object for investigating how lactose and galactose metabolism are regulated because it has long become a model system for biochemical and genetic research on fungi, and mutants in the lactose-metabolizing pathway of A. nidulans are available. In this paper, we will review the contributions of our research group achieved on this field.


The contribution of Trichoderma to balancing the costs of plant growth and defense.
Trichoderma is a fungal genus of cosmopolitan distribution and high biotechnological value, with several species currently used as biological control agents. Additionally, the enzyme systems of the fungus are widely applied in industry. Species of Trichoderma protect plants against the attack of soil-borne plant pathogens by competing for nutrients and inhibiting or killing plant pathogenic fungi and oomycetes, through the production of antibiotics and/or hydrolytic enzymes. In addition to the role of Trichoderma spp. as biocontrol agents, they have other beneficial effects on plants, including the stimulation of plant defenses and the promotion of plant growth. In this review, we focus on the complex plant defense signaling network that allows the recognition of fungi as non-hostile microbes, including microbial-associated molecular patterns (MAMPs), damage-associated molecular patterns (DAMPs) and secreted elicitors. We also examine how fungal interactions with plant receptors can activate induced resistance by priming and balancing plant defense and growth responses. Our observations are integrated into a model describing Trichoderma-plant hormone signaling network interactions.


Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi.
Regulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacological tools, the research reported here aims to characterize new marine compounds acting as RCD modulators. Protein kinases (PKs) are key signaling actors in various RCDs notably through the control of either mitosis (e.g., the PKs Aurora A and B) or necroptosis (e.g., RIPK1 and RIPK3). From the primary screening of 27 various extracts of marine organisms collected in the Mediterranean Sea, an extract and subsequently a purified high molecular weight compound dubbed P3, were isolated from the marine sponge Crambe tailliezi and characterized as a selective inhibitor of PKs Aurora A and B. Furthermore, P3 was shown to induce apoptosis and to decrease proliferation and mitotic index of human osteosarcoma U-2 OS cells.


Patient Engagement in and Adaptations to Delivery of Outpatient Care for Opioid Use Disorder During the COVID-19 Pandemic.
The authors investigated adaptations to outpatient care delivery and changes in treatment demand and engagement among patients receiving medications for opioid use disorder (MOUD) in the months after the declaration of the COVID-19 public health emergency in 2020. Data were collected through an online survey (June-November 2020) of outpatient MOUD prescribers. The survey obtained information on outpatient practices' adaptations to MOUD treatment and urine drug screening (UDS) and elicited provider views on the effects of the COVID-19 pandemic on patient demand for, and engagement in, treatment. Multivariable regression analyses were used to examine associations among practice characteristics, patient engagement, and service adaptations. Of 516 respondents, 74% reported adaptations to MOUD delivery during the pandemic. Most respondents implemented virtual visits for initial (67%) and follow-up (77%) contacts. Prescribers of buprenorphine were more likely than those who did not prescribe the medication to report MOUD adaptations. Among respondents reporting any MOUD adaptation, 77% made adaptations to their UDS practices. Among 513 respondents who answered COVID-19-related questions, 89% reported that the pandemic had affected the treatment and engagement of their patients. Of these respondents, 30% reported increased difficulty with patient engagement, and 45% reported that their patients preferred virtual visits during this period, whereas 18% endorsed patient preference for in-person visits. Telehealth and federal regulatory easements in response to the COVID-19 pandemic enabled providers to continue treating patients for opioid use disorder in 2020. The results suggest that care adaptations and changes in patient demand and engagement were common in the practices surveyed.


Readers of the m6A epitranscriptomic code.
N6-methyl adenosine (m6A) is the most prevalent and evolutionarily conserved, modification of polymerase II transcribed RNAs. By post-transcriptionally controlling patterns of gene expression, m6A deposition is crucial for organism reproduction, development and likely stress responses. m6A mostly mediates its effect by recruiting reader proteins that either directly accommodate the modified residue in a hydrophobic pocket formed by their YTH domain, or otherwise have their affinity positively influenced by the presence of m6A. We firstly describe here the evolutionary history, and review known molecular and physiological roles of eukaryote YTH readers. In the second part, we present non YTH-proteins whose roles as m6A readers largely remain to be explored. The diversity and multiplicity of m6A readers together with the possibility to regulate their expression and function in response to various cues, offers a multitude of possible combinations to rapidly and finely tune gene expression patterns and hence cellular plasticity. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.


Effect of starvation on protein synthesis in neonatal rat liver.
Hepatic protein synthesis was measured in vivo and in vitro (liver slice) in 6- and 19-day-old rats. Fed and 15-hour starved rats were compared in each individual experiment. The study demonstrated that in the 6-day-old rat, hepatic protein synthesis is very sensitive to restrictions in dietary influx. In contrast, no significant differences in protein synthesis were detected when 19-day-old rats were fasted for 15 hours. In the fed state, the protein synthetic activity of the tissue unit was the same irrespective of age. Thus, it appears that it is not the maximal capacity for protein synthesis that changes with age, but rather the extent to which the system can adapt to the changing nutritional environment.


Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis.
Aortic stenosis (AS) results in myocyte and extracellular matrix remodeling in the human left ventricle (LV). The myocardial renin-angiotensin system is activated and collagens I and III and fibronectin accumulate. We determined the yet unknown regulation of enzymes that control collagen turnover, i.e., LV matrix metalloproteinases (MMP) and their tissue inhibitors (TIMPs) in human AS. We compared LV samples from AS patients undergoing elective aortic valve replacement (n=19) with nonused donor hearts with normal LV function (controls, n=12). MMP-2, MMP-9, MT1-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN), TIMP-1, TIMP-2, TIMP-3, and TIMP-4 mRNA were quantitated by real-time RCR. MMP-1, MMP-2, MMP-3, TIMP-3, TIMP-4, and EMMPRIN protein were measured by immunoblotting and MMP-9 and TIMP-1 protein by ELISA. Gelatinolytic MMP-2 and MMP-9 activity was measured by zymography. MMP-2 was increased in AS at mRNA, protein, and activity levels (131%, 193%, and 138% of controls). MMP-3 protein (308%) and EMMPRIN mRNA and protein were also upregulated (171% and 200%). In contrast, MMP-1 (37%) and MMP-9 mRNA, protein, and activity (26%, 21%, and 52%) were downregulated. MMP-9 activity was inversely correlated with LV size. TIMP-1 mRNA and protein were decreased (55% and 73%). In contrast, TIMP-2 mRNA (358%), TIMP-3 mRNA and protein (145% and 249%) were increased. TIMP-4 mRNA was not altered, but TIMP-4 protein was upregulated to 350%. Changes were similar in AS patients with normal and impaired LV ejection fraction. The dysregulation of myocardial MMPs and TIMPs in human AS starts at an early disease stage when LV function is still normal. In spite of upregulation of some MMPs the balance between MMP and TIMP is shifted towards MMP inhibition in human AS and may contribute to collagen accumulation.


Aggressive Surgical Therapy With Early Vitrectomy, Panretinal Photocoagulation, and Silicone Oil Tamponade for Streptococcus mitis Endophthalmitis.
An 87-year-old woman presented with acute, painful vision loss in her right eye after intravitreal injection. Examination disclosed hypopyon and vitritis, as well as discrete inflammatory collections in the vitreous and widespread retinal hemorrhages. The patient underwent vitrectomy with injection of intravitreal antibiotics. Vitreous cultures were positive for Streptococcus mitis, a pathogen associated with severe tissue damage and poor clinical outcomes. Clinical deterioration prompted repeat vitrectomy with silicone oil tamponade and panretinal photocoagulation two weeks later, resulting in more favorable anatomic and visual outcomes. Endophthalmitis caused by exotoxin-producing bacterial species such as S. mitis is often associated with severe vision loss or loss of the eye. Aggressive surgical intervention--prompted by concerning clinical findings and vitreous cultures--may play a role in improving outcomes in these patients.


Distal myopathies.
The distal myopathies are a heterogeneous group of disorders that pose a challenge to both the clinician and geneticist. This article summarizes the findings of recent clinical, genetic and molecular studies and the current diagnostic approach to this group of patients. Publications over the past 5 years describe a number of new clinical phenotypes and genetic loci and further emphasize the overlap in clinical phenotype between a number of these disorders and between the distal and limb girdle myopathies and hereditary inclusion body myopathies. Recent studies have led to the identification of the genes and mutations responsible for early onset (Laing) myopathy and tibial (Udd) myopathy, and for distal myopathy with rimmed vacuoles (Nonaka), which has been shown to be allelic with quadriceps sparing hereditary inclusion body myopathy (IBM2), and have elucidated the underlying pathogenetic mechanisms in these conditions. New diagnostic approaches using magnetic resonance imaging, and a blood-based assay for dysferlin deficiency, have also been reported. These findings have important implications for future genetic linkage and gene expression studies and for the diagnostic approach to patients with a distal myopathy phenotype. They also hold promise for the eventual development of therapies for this group of disorders.


Treatment with flutamide decreases cortisol clearance: implications for therapy in congenital adrenal hyperplasia.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by a defect in cortisol and often aldosterone secretion, and adrenal hyperandrogenism. Current treatment is to provide adequate glucocorticoid and mineralocorticoid substitution to prevent adrenal crises and to suppress excess adrenocortical androgen secretion. Anti-androgen therapy with flutamide is an option that allows control of hyperandrogenism without recourse to supraphysiological doses of glucocorticoid. We examined the pharmacokinetic parameters of hydrocortisone administered i.v. as a bolus at a dose of 15 mg/m2 in a 17.3 year-old female patient with classic CAH before and four weeks after institution of flutamide treatment by determining serum cortisol concentrations at 10 min intervals for 6 h following the i.v. bolus of hydrocortisone. Treatment with flutamide resulted in a decrease in cortisol clearance from 420 ml/l to 305 ml/l (27% reduction), and a decrease in volume of distribution from 51.61 to 451 (12.9% reduction). The half-life of cortisol increased from 85.3 min to 102.1 min. Flutamide treatment decreases cortisol clearance, thereby prolonging its half-life. These findings indicate that a reduction in the daily dose of glucocorticoid replacement may need to be considered when flutamide is added to the treatment regimen of patients receiving hydrocortisone.


An intraocular foreign body masquerading as idiopathic chronic iridocyclitis.
The authors report a case of presumed idiopathic chronic iridocyclitis in which an intraocular foreign body (IOFB) was finally identified. There was no history of prior eye trauma. Ophthalmologic and laboratory evaluations were inconclusive. Seven months following unsuccessful medical treatment of the iritis and given the patient's occupational history, a skull x-ray was performed followed by computed tomography of the orbits. A metallic IOFB was identified in the pars plicata and was surgically removed with resolution of the inflammation. The possibility of an IOFB should always be entertained in idiopathic iridocyclitis refractory to medical treatment, even when there is no history of ocular trauma.


Renal antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.
Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis. Diabetes was induced in 28 Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin. Control rats (n = 10) received only buffer solution. An ACE inhibitor (ramipril, 3 mg/kg/day) was administered to 11 diabetic rats. After 2 months, Ac-SDKP (1 mg/kg/day) was administered by osmotic minipumps for 8 weeks to 7 diabetic rats and to 6 diabetic rats treated with ramipril. Osmotic minipumps delivered saline solution in the corresponding sham-treated rats (diabetic rats, n = 10, and ramipril-treated diabetic rats, n = 5). Diabetic rats showed a significant increase in blood glucose level, urinary albumin excretion and renal fibrosis, and a reduction of glomerular nephrin expression with respect to control rats. Ac-SDKP administration significantly reduced renal fibrosis in diabetic rats, without significantly reducing urinary albumin excretion. Ramipril treatment caused a significant decrease in albuminuria and renal fibrosis and restored glomerular nephrin expression. Administration of Ac-SDKP, in addition to ramipril, further reduced renal fibrosis with respect to ramipril alone, while it did not improve the antiproteinuric effect of ramipril. Ac-SDKP administration reduces renal fibrosis in diabetic nephropathy. Addition of Ac-SDKP to ACE inhibition therapy improves the reduction of renal fibrosis with respect to ACE inhibition alone, suggesting a beneficial effect of this pharmacological association in diabetic nephropathy.


Catalysis of the Water Oxidation Reaction in the Presence of Iron and a Copper Foil.
The oxygen evolution reaction (OER) can provide electrons for reducing water, carbon dioxide, and ammonia. On the other hand, copper compounds are among the most interesting OER catalysts. In this study, water oxidation of a Cu foil in the presence of K2FeO4, a soluble Fe source, under alkaline conditions (pH ≈ 13) is investigated using electrochemical methods, X-ray diffraction, X-ray photoelectron spectroscopy, in situ visible spectroelectrochemistry, Raman spectroscopy, and scanning electron microscopy. After the reaction of the Fe salt with the Cu foil, a remarkable improvement for OER is recorded, which indicates that either the Fe ions on the copper foil directly participate in OER or these ions are critical for activating copper ions on the surface toward OER. Indeed, a remarkable decrease (130 mV) in the overpotential is recorded for the Cu foil in the presence of [FeO4]2-. Tafel slopes for the Cu foil in the absence and presence of K2FeO4 are 113.2 and 46.4 mV/decade, respectively. X-ray photoelectron spectroscopy shows that there is a strong interaction between Cu(II) and Fe(III) on the surface of the Cu foil. During OER in the presence of Cu(II) (hydr)oxide, Cu(III) is detected. In situ visible spectroelectrochemistry shows that Cu and Fe ions are dynamically active and precipitate on the surface of the counter electrode during cyclic voltammetry (CV). The isotopic experimental data using H218O based on Raman spectroscopy show that there is no change in the lattice oxygen. All of these experiments adopt a new perspective on the role of Fe in OER in the presence of a Cu foil under alkaline conditions.


[Study designs].
Methods design follows object design. The study question defines which study design is most appropriate. The ideal study design provides the most valid results. Sometimes, practicality reasons or costs (efficiency) impede using the ideal design. Researchers need to weigh the consequences of suboptimal design elements against the risk of bias.


Formation of Exotic Networks of Water Clusters in Helium Droplets Facilitated by the Presence of Neon Atoms.
Water clusters are formed in helium droplets via the sequential capture of monomers. One or two neon atoms are added to each droplet prior to the addition of water. The infrared spectrum of the droplet ensemble reveals several signatures of polar, water tetramer clusters having dipole moments between 2D and 3D. Comparison with ab initio computations supports the assignment of the cluster networks to noncyclic "3 + 1" clusters, which are ∼5.3 kcal/mol less stable than the global minimum nonpolar cyclic tetramer. The (H2O)3Ne + H2O ring insertion barrier is sufficiently large, such that evaporative helium cooling is capable of kinetically quenching the nonequilibrium tetramer system prior to its rearrangement to the lower energy cyclic species. To this end, the reported process results in the formation of exotic water cluster networks that are either higher in energy than the most stable gas-phase analogs or not even stable in the gas phase.


Enhanced beta 2-microglobulin levels in lymphocyte culture supernatants from patients with idiopathic nephrotic syndrome: inhibition of lymphocyte activation by cyclosporine.
Idiopathic nephrotic syndrome (INS) is associated with a disorder of T-lymphocyte function, and an enhanced production of a vasoactive lymphokine, the vascular permeability factor (VPF). In an attempt to evaluate lymphocyte activation in various phases of INS, we measured beta 2-microglobulin (beta 2m) levels in lymphocyte culture supernatants (LCS). In 23 cases of untreated active INS, beta 2m levels in unstimulated LCS were significantly increased in comparison with those of 13 cases of untreated INS in complete remission (p less than 0.001), of 17 cases of active membranous nephropathy (p less than 0.01) and of 14 controls (p less than 0.001). In 13 patients treated with cyclosporine (Cs) (3-4.5 mg/kg/d) during 3 months, beta 2m levels were within the normal range. Although the beta 2m of 7 Cs patients without proteinuria was lower than 5 Cs patients with residual proteinuria, the difference was not statistically significant. In 15 prednisone(Pr)-treated INS patients, beta 2m levels were normalized. However their beta 2m levels were lower in 8 cases of complete remission than in 7 cases of persistent proteinuria (p less than 0.05). Concanavalin-A stimulation increased beta 2m amounts in all groups with a similar magnitude. In vitro addition of Cs (100 ng/ml) inhibited both beta 2m and VPF elevations observed in active INS. beta 2m level and VPF activity were significantly correlated (r = 0.54, p less than 0.01). High levels of beta 2m in LCS from INS are the consequence of an enhanced cellular synthesis and they are inhibited by Pr and Cs. Thus beta 2m increase in INS indeed reflects lymphocyte activation.


Potassium channel dysfunction in neurons and astrocytes in Huntington's disease.
Huntington's disease (HD) is a late-onset fatal neurodegenerative disease, characterized by progressive movement disorders, psychiatric symptoms, and cognitive impairment. The cytosine-adenine-guanine (CAG) triplet expansion encoding glutamine present in the protein huntingtin (Htt), produces widespread neuronal and glial pathology. Mutant huntingtin (mHtt) nuclear aggregates are the primary cause of cortical and striatal neuron degeneration, neuronal inflammation, apoptosis and eventual cell loss. The precise mechanisms underlying the pathogenesis of neurodegeneration in HD remain poorly understood and HD patients have no current cure. Potassium channels are widely expressed in most cell types. In neurons, they play a crucial role in setting the resting membrane potential, mediating the rapid repolarization phase of the action potential and controlling sub-threshold oscillations of membrane potentials. In glial cells, their major contributions are maintaining the resting membrane potential and buffering extracellular K+ . Thus, potassium channels have an essential function in both physiological and pathological brain conditions. This review summarizes recent progress on potassium channels involved in the pathology of HD by using different HD mouse models. Exploring the dysfunction of potassium channels in the brain illustrates new approaches for targeting this channel for the treatment of HD.


Classification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration.
Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. Multicenter retrospective analysis. Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy. Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models. Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05). Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


The validity, reliability and responsiveness of the Nottingham Extended Activities of Daily Living scale in patients undergoing total hip replacement.
The Nottingham Extended Activities of Daily Living (EADL) scale is a popular outcome measure in stroke research. Its psychometric properties have not been tested in other conditions. EADL has been measured before, three and six months after hip arthroplasty. A sample was retested for reliability. Comparisons were made with the SF-36 and London Handicap Scale. Standard psychometric parameters were calculated. The sub-scales and total score were approximately unidimensional on factor analysis and Cronbach's alpha, but did not form an adequate hierarchical (Guttmann) scale. Associations with other scales were in the expected direction and of approximately the expected strength, supporting concurrent and construct validity. Reliability was good. Responsiveness was poor compared with the other scales. The EADL is valid in patients with arthritis of the hip, and is reliable. However, it underestimates the size of health gain after hip arthroplasty compared with other scales.


A case of hydrops fetalis due to placental chorioangioma.
A case of an infant born in association with a large chorioangioma of the placenta is reported. The mother was complicated with polyhydramnios and premature labor. The fetal complications were congestive heart failure and hydrops fetalis. This case serves to emphasize that it is necessary to examine the placenta in every perinatal autopsy case.


Chaperones in Neurodegeneration.
Cellular protein homeostasis (proteostasis) maintains the integrity of the proteome and includes protein synthesis, folding, oligomerization, and turnover; chaperone proteins assist with all of these processes. Neurons appear to be especially susceptible to failures in proteostasis, and this is now increasingly recognized as a major origin of neurodegenerative disease. This review, based on a mini-symposium presented at the 2015 Society for Neuroscience meeting, describes new work in the area of neuronal proteostasis, with a specific focus on the roles and therapeutic uses of protein chaperones. We first present a brief review of protein misfolding and aggregation in neurodegenerative disease. We then discuss different aspects of chaperone control of neuronal proteostasis on topics ranging from chaperone engineering, to chaperone-mediated blockade of protein oligomerization and cytotoxicity, to the potential rescue of neurodegenerative processes using modified chaperone proteins. Aberrant protein homeostasis within neurons results in protein misfolding and aggregation. In this review, we discuss specific roles for protein chaperones in the oligomerization, assembly, and disaggregation of proteins known to be abnormally folded in neurodegenerative disease. Collectively, our goal is to identify therapeutic mechanisms to reduce the cellular toxicity of abnormal aggregates.


First detection of Ehrlichia minasensis in Hyalomma marginatum ticks collected from cattle in Corsica, France.
Ehrlichiosis are severe, feverish tick-borne illnesses caused by specific species within the genus Ehrlichia (Anaplasmataceae family). Recent data suggest that ruminants in Corsica area reservoir for several Anaplasmataceae species. The purpose of our study was to determine whether Ehrlichia species could be detected in ticks collected in Corsican ruminants by using molecular methods. Ticks were collected in northern Corsica: (i) in May 2016 from sheep bred in one farm located in a 5000-inhabitants village and (ii) from cattle in June and July 2016 in a slaughterhouse. There sheep and cattle whole skin was inspected and ticks were collected manually. A total of 647 ticks was collected in northern Corsica during this study: 556 (86%) belonged to the Rhipicephalus bursa species and 91 (14%) to Hyalomma marginatum. The 91 H. marginatum ticks were organized in 27 pools, of which one (3.7%) was found positive for the presence of E. minasensis; this pool consisted of six ticks collected from a cow bred and raised northwestern Corsica. Ehrlichial DNA was not detected in R. bursa ticks. The 16S rRNA and groEL gene sequences of Ehrlichia detected in the H. marginatum pool showed 100% (303/303 bp) and 99.8% (555/556) of nucleotide identity with E. minasensis, respectively. Phylogenetic analyses demonstrated the highest closeness with E. minasensis UFMG-EV genotype than to any other E. canis strains. To our knowledge, this is the first report of E. minasensis outside of Brazil, Ethiopia and Canada. This identification of E. minasensis in H. marginatum merits to be further investigated and pleads for translational studies addressing the potential impact of vector-borne diseases of human and veterinary impact through large-scale research and surveillance programmes in Corsica.


Acute, subchronic toxicity and genotoxicity studies of JointAlive, a traditional Chinese medicine formulation for knee osteoarthritis.
In vivo and in vitro toxicity tests of JointAlive® were studied in animal models to support the safe use of JointAlive® as a drug for knee osteoarthritis treatment. The acute toxicity study in Sprague Dawley (SD) rats was conducted at a 20 g/kg bw/day dose of JointAlive®. For 13-week subchronic toxicity tests, SD rats were orally dosed daily with 0.5, 1.5 and 5 g/kg bw/day of JointAlive®. To assess the potential genotoxicity, Ames test, cellular chromosome aberration and mouse micronucleus test in vivo were carried out. Based on a lack of notable findings other than histopathology finding of co-incidental prostate inflammation at the high dose, the "No Observed Adverse Effect Level (NOAEL)" of JointAlive® was concluded as 5 g/kg bw/day in males and females. Results also indicated that JointAlive® has no risk of genotoxicity. General toxicity and genotoxicity studies empirically demonstrated that JointAlive® poses a low risk of potential health risks, providing safety supports for the application of JointAlive® as a potential drug candidate to treat knee osteoarthritis.


Lateral acquisition of genes is affected by the friendliness of their products.
A major factor in the evolution of microbial genomes is the lateral acquisition of genes that evolved under the functional constraints of other species. Integration of foreign genes into a genome that has different components and circuits poses an evolutionary challenge. Moreover, genes belonging to complex modules in the pretransfer species are unlikely to maintain their functionality when transferred alone to new species. Thus, it is widely accepted that lateral gene transfer favors proteins with only a few protein-protein interactions. The propensity of proteins to participate in protein-protein interactions can be assessed using computational methods that identify putative interaction sites on the protein. Here we report that laterally acquired proteins contain significantly more putative interaction sites than native proteins. Thus, genes encoding proteins with multiple protein-protein interactions may in fact be more prone to transfer than genes with fewer interactions. We suggest that these proteins have a greater chance of forming new interactions in new species, thus integrating into existing modules. These results reveal basic principles for the incorporation of novel genes into existing systems.