An in vivo control map for the eukaryotic mRNA translation machinery

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis

A triple-strand anatomic medial collateral ligament reconstruction restores knee stability more completely than a double-strand reconstruction: a biomechanical study in vitro.

BACKGROUND: There are many descriptions of medial collateral ligament (MCL) reconstruction, but they may not reproduce the anatomic structures and there is little evidence of their biomechanical performance. PURPOSE: To investigate the ability of "anatomic" MCL reconstruction to restore native stability after grade III MCL plus posteromedial capsule/posterior oblique ligament injuries in vitro. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve cadaveric knees were mounted in a kinematic testing rig to impose tibial displacing loads while the knee was flexed-extended: 88-N anteroposterior translation, 5-N·m internal-external rotation, 8-N·m valgus-varus, and combined anterior translation plus external rotation (anteromedial rotatory instability). Joint motion was measured via optical trackers with the knee intact; after superficial MCL (sMCL), deep MCL (dMCL), and posterior oblique ligament transection; and then after MCL double- and triple-strand reconstructions. Double strands reproduced the sMCL and posterior oblique ligament and triple-strands the sMCL, dMCL, and posterior oblique ligament. The sMCL was placed 5 mm posterior to the epicondyle in the double-strand technique and at the epicondyle in the triple-strand technique. Kinematic changes were examined by repeated measures 2-way analysis of variance with posttesting. RESULTS: Transection of the sMCL, dMCL, and posterior oblique ligament increased valgus rotation (5° mean) and external rotation (9° mean). The double-strand reconstruction controlled valgus in extension but allowed 5° excess valgus in flexion and did not restore external rotation (7° excess). The triple-strand reconstruction restored both external rotation and valgus throughout flexion. CONCLUSION: In a cadaveric model, a triple-strand reconstruction including a dMCL graft restored native external rotation, while a double-strand reconstruction without a dMCL graft did not. A reconstruction with the sMCL graft placed isometrically on the medial epicondyle restored valgus rotation across the arc of knee flexion, whereas a reconstruction with a more posteriorly placed sMCL graft slackened with knee flexion. CLINICAL RELEVANCE: An MCL injury may rupture the anteromedial capsule and dMCL, causing anteromedial rotatory instability. Persistent MCL instability increases the likelihood of ACL graft failure after combined injury. A reconstruction with an anteromedial dMCL graft restored native external rotation, which may help to unload/protect an ACL graft. It is important to locate the sMCL graft isometrically at the femoral epicondyle to restore valgus across flexion

Co-assembly of chitosan and phospholipids into hybrid hydrogels

Novel hybrid hydrogels were formed by adding chitosan (Ch) to phospholipids (P) self-assembled particles in lactic acid. The effect of the phospholipid concentration on the hydrogel properties was investigated and was observed to affect the rate of hydrogel formation and viscoelastic properties. A lower concentration of phospholipids (0.5% wt/v) in the mixture, facilitates faster network formation as observed by Dynamic Light Scattering, with lower elastic modulus than the hydrogels formed with higher phospholipid content. The nano-porous structure of Ch/P hydrogels, with a diameter of 260±20 nm, as observed by cryo-scanning electron microscopy, facilitated the penetration of water and swelling. Cell studies revealed suitable biocompatibility of the Ch/P hydrogels that can be used within life sciences applications

All different or all the same? Exploring the diversity of professional practices in Portuguese school psychology

"Published online: 29 March 2016"Studies have generally characterized school psychologists as a relative homogenous population. Understanding the differences in professional practices and related variables is important for the development of the profession. Using a sample of 446 Portuguese school psychologists, this study used cluster analysis to identify distinct profiles of professional activity, based on practitioners’ time distribution among different target audiences (i.e.,students, parents, teachers, school board members, school non-professional staff, and other professionals within the school community). Three distinct profiles emerged from the data: a group highly oriented to work with students, a group that distributes time almost equitably between adults and students, and a group that concentrates attention and professional expertise on adults. Practice setting variables, such as school-psychologists-to-student ratio, schoolpsychologists-to-school ratio, number of referrals per year, and school community level of demand for different activities, were found to be significantly related to cluster membership. No personal- or professional-background-related variables differentiated the three groups. The main implications of these findings are discussed in light of recent literature regarding the models of service delivery for school psychologists

Metformin-induced lactic acidosis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin.</p> <p>Case presentation</p> <p>We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed and he was discharged from the intensive care unit on the seventh day.</p> <p>Conclusion</p> <p>We present two case reports of severe lactic acidosis most probably associated with high doses of metformin in patients with no known contraindications for metformin prescription. In both patients no other condition was identified to cause such severe lactic acidosis. Although controversial, lactic acidosis should be considered in patients taking metformin.</p

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets