Glucuronoyl esterases - enzymes to decouple lignin and carbohydrates and enable better utilization of renewable plant biomass

Glucuronoyl esterases (GEs) are microbial enzymes able to cleave covalent linkages between lignin and carbohydrates in the plant cell wall. GEs are serine hydrolases found in carbohydrate esterase family 15 (CE15), which belongs to the large α/β hydrolase superfamily. GEs have been shown to reduce plant cell wall recalcitrance by hydrolysing the ester bonds found between glucuronic acid moieties on xylan polysaccharides and lignin. In recent years, the exploration of CE15 has broadened significantly and focused more on bacterial enzymes, which are more diverse in terms of sequence and structure to their fungal counterparts. Similar to fungal GEs, the bacterial enzymes are able to improve overall biomass deconstruction but also appear to have less strict substrate preferences for the uronic acid moiety. The structures of bacterial GEs reveal that they often have large inserts close to the active site, with implications for more extensive substrate interactions than the fungal GEs which have more open active sites. In this review, we highlight the recent work on GEs which has predominantly regarded bacterial enzymes, and discuss similarities and differences between bacterial and fungal enzymes in terms of the biochemical properties, diversity in sequence and modularity, and structural variations that have been discovered thus far in CE15

An Investigation of the Qualities, Knowledge, and Skills of Effective Teachers for Students with Emotional/Behavioral Disorders: The Teacher Perspective

This study investigated the qualities, knowledge, and skills of effective teachers for students with emotional/behavioral disorders (EBD) from the perspective of six special education teachers. Data were collected using semi-structured interviews and a focus group. An analysis of the data yielded three themes. First, effective EBD teachers develop unconditional teacher- student relationships. No matter how many setbacks a student with EBD may experience, the effective EBD teacher relentlessly affirms his or her belief in the student’s ability to succeed. Second, effective EBD teachers create positive classroom environments. When students with EBD are removed from the general education setting or experience a crisis at school, the effective EBD teacher provides a safe, consistent, and nonjudgmental haven. Finally, effective EBD teachers individualize instruction. Having knowledge of behavioral disorders and effective strategies is insufficient. The effective EBD teacher identifies the unique needs of each student and designs instruction that meets students’ individual academic and behavioral needs

The Effects of Naltrexone Among Alcohol Non-Abstainers: Results from the COMBINE Study

These analyses of the COMBINE Study examined the effects of naltrexone among non-abstainers. Given that one of the most well-established mechanisms of action of naltrexone involves blunting of alcohol reward, it is hypothesized that naltrexone should be more effective among individuals who drank during treatment. Participants were 952 (78% of the total COMBINE Study sample) treatment-seeking alcohol-dependent men and women who received pharmacotherapy for alcoholism and drank at least once during the 16-week trial. Mixed model analyses revealed that individuals who drank more regularly during the trial seemed to benefit most from naltrexone and the effects of naltrexone on heavy drinking was significant in treatment months 2 through 4 among individuals who reported drinking on 81, 68, and 60% or more of days, respectively. Those drinking frequencies were observed in 11, 15, and 19% of the sample. Similar effects were not observed for drinks per drinking day. These results suggest that a small subgroup of non-abstainers, composed primarily of very regular drinkers, appears to benefit from naltrexone in reducing heavy drinking days. Naltrexone may be effective in the context of controlled-drinking approaches, even among very frequent drinkers

Toward a consensus nomenclature for ghrelin, its non-acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor

The stomach-derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward-related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non-acylated form of ghrelin, desacyl-ghrelin, can also be detected in biological samples. Desacyl-ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well-characterized than that of ghrelin. Ghrelin and desacyl-ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms “ghrelin” and “desacyl-ghrelin” to refer to the hormone itself and its non-acylated form, respectively. Based on the results of this consensus, we further propose using the terms “GHSR” for the receptor, and “LEAP2” for liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Dickson, Suzanne L.. The Sahlgrenska Academy at the University of Gothenburg; SueciaFil: Zigman, Jeffrey M.. UT Southwestern Medical Center; Estados UnidosFil: Leggio, Lorenzo. National Institutes of Health; Estados Unido

Cutaneous manifestations in celiac disease

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed

Correlation of Formative Assessments as the Means of Predicting Summative Performance in Paramedic Students

Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam. Methods: Formative and summative scores from 2011 - 2016 for paramedic students with accounts in Fisdap, an Internet-based administrative database, were retrospectively reviewed for the following criteria: provided consent for research, completed all six formative (unit) examinations, and completed a summative (comprehensive) examination. Analyses were performed with Pearson correlations and linear regression. Results: A total of 1,406 student records were included based on inclusion criteria. Correlation with each formative and the summative examination were all significant, p \u3c0.001: Cardiology 0.597; Airway 0.571; Medical 0.571; Trauma 0.566; Ob/Pediatrics 0.549; Operations 0.495. The cardiology exam was shown to have a moderate correlation on summative performance, whereas the operations exam had the weakest correlation. The number of formative examination failures was a significant predictor of the probability of passing the summative examination, t(1405) - -31.02 p\u3c0.001. Zero failed unit examinations yielded a 100% probability of passing. Three failed formative exams yielded a 60.4% probability. Four failed attempts yielded a 44.8% probability. Failure of all six formative exams yielded a 13.4% probability of passing the Paramedic Readiness Exam Version 3. Conclusion: Not all formative examinations hold the same predictive power on the probability of passing a summative examination. Each had their own correlation value. Students who did not fail formative examinations have a 100% likelihood of passing the summative examination

Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a wilson disease patient with hepatic presentation, anxiety and spect abnormalities

Wilson disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD- SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson disease. Since most of Wilson disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson disease therapy, and in particular to differentiate specific therapies for different Wilson disease phenotypes

Correlation of formative assessments as the means of predicting summative performance in paramedic students

Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed formative units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam. Methods: Formative and summative scores from 2011 – 2016 for paramedic students with accounts in Fisdap™, an Internet-based administrative database, were retrospectively reviewed for the following criteria: provided consent for research, completed all six formative (unit) examinations, and completed a summative (comprehensive) examination. Analyses were performed with Pearson correlations and linear regression. Results: A total of 1,406 student records were included based on inclusion criteria. Correlation with each formative and the summative examination were all significant, p \u3c 0.001: Cardiology 0.597; Airway 0.571; Medical 0.571; Trauma 0.566; Ob/Pediatrics 0.549; Operations 0.495. The cardiology exam was shown to have a moderate correlation on summative performance, whereas the operations exam had the weakest correlation. The number of formative examination failures was a significant predictor of the probability of passing the summative examination, t(1405) = –31.02, p \u3c 0.001. Zero failed unit examinations yielded a 100% probability of passing. Three failed formative exams yielded a 60.4% probability. Four failed attempts yielded a 44.8% probability. Failure of all six formative exams yielded a 13.4% probability of passing the Paramedic Readiness Exam Version 3. Conclusion: Not all formative examinations hold the same predictive power on the probability of passing a summative examination. Each had their own correlation value. Students who did not fail formative examinations have a 100% likelihood of passing the summative examination

Spontaneous central venous thrombosis and shunt occlusion following peritoneovenous shunt placement for intractable ascites

A 43-year-old man had a peritoneovenous shunt inserted for the treatment of chylous ascites secondary to myelofibrosis. Despite being on anticoagulation for superior mesenteric vein thrombosis, he developed shunt dysfunction within two weeks of insertion. Superior venacavography showed multiple filling defects in the right axillary vein, no filling of the right brachiocephalic and right subclavian vein, and thrombotic occlusion of the internal jugular veins bilaterally. The shunt was removed 11 days after insertion, and there was extensive thrombosis of the venous end of the shunt and the compressible pump chamber. Shunt thrombosis is known to occur but remains a rare complication, with 87% of such obstructions being due to a thrombus at the tip of the venous end of the shunt. Extensive thrombosis of the shunt (as in the present case) is very rare

Structural and Functional Analysis of a Multimodular Hyperthermostable Xylanase-Glucuronoyl Esterase from Caldicellulosiruptor kristjansonii

The hyperthermophilic bacterium Caldicellulosiruptor kristjansonii encodes an unusual enzyme, CkXyn10C-GE15A, which incorporates two catalytic domains, a xylanase and a glucuronoyl esterase, and five carbohydrate-binding modules (CBMs) from families 9 and 22. The xylanase and glucuronoyl esterase catalytic domains were recently biochemically characterized, as was the ability of the individual CBMs to bind insoluble polysaccharides. Here, we further probed the abilities of the different CBMs from CkXyn10C-GE15A to bind to soluble poly- and oligosaccharides using affinity gel electrophoresis, isothermal titration calorimetry, and differential scanning fluorimetry. The results revealed additional binding properties of the proteins compared to the former studies on insoluble polysaccharides. Collectively, the results show that all five CBMs have their own distinct binding preferences and appear to complement each other and the catalytic domains in targeting complex cell wall polysaccharides. Additionally, through renewed efforts, we have achieved partial structural characterization of this complex multidomain protein. We have determined the structures of the third CBM9 domain (CBM9.3) and the glucuronoyl esterase (GE15A) by X-ray crystallography. CBM9.3 is the second CBM9 structure determined to date and was shown to bind oligosaccharide ligands at the same site but in a different binding mode compared to that of the previously determined CBM9 structure from Thermotoga maritima. GE15A represents a unique intermediate between reported fungal and bacterial glucuronoyl esterase structures as it lacks two inserted loop regions typical of bacterial enzymes and a third loop has an atypical structure. We also report small-angle X-ray scattering measurements of the N-terminal CBM22.1-CBM22.2-Xyn10C construct, indicating a compact arrangement at room temperature