A Naturally Occurring Plant Cysteine Protease Possesses Remarkable Toxicity against Insect Pests and Synergizes Bacillus thuringiensis Toxin

When caterpillars feed on maize (Zea maize L.) lines with native resistance to several Lepidopteran pests, a defensive cysteine protease, Mir1-CP, rapidly accumulates at the wound site. Mir1-CP has been shown to inhibit caterpillar growth in vivo by attacking and permeabilizing the insect's peritrophic matrix (PM), a structure that surrounds the food bolus, assists in digestion and protects the midgut from microbes and toxins. PM permeabilization weakens the caterpillar defenses by facilitating the movement of other insecticidal proteins in the diet to the midgut microvilli and thereby enhancing their toxicity. To directly determine the toxicity of Mir1-CP, the purified recombinant enzyme was directly tested against four economically significant Lepidopteran pests in bioassays. Mir1-CP LC50 values were 1.8, 3.6, 0.6, and 8.0 ppm for corn earworm, tobacco budworm, fall armyworm and southwestern corn borer, respectively. These values were the same order of magnitude as those determined for the Bacillus thuringiensis toxin Bt-CryIIA. In addition to being directly toxic to the larvae, 60 ppb Mir1-CP synergized sublethal concentrations of Bt-CryIIA in all four species. Permeabilization of the PM by Mir1-CP probably provides ready access to Bt-binding sites on the midgut microvilli and increases its activity. Consequently, Mir1-CP could be used for controlling caterpillar pests in maize using non-transgenic approaches and potentially could be used in other crops either singly or in combination with Bt-toxins

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

Incidence and prevalence of patellofemoral pain: a systematic review and meta-analysis

Background: Patellofemoral pain is considered one of the most common forms of knee pain, affecting adults, adolescents, and physically active populations. Inconsistencies in reported incidence and prevalence exist and in relation to the allocation of healthcare and research funding, there is a clear need to accurately understand the epidemiology of patellofemoral pain. Methods: An electronic database search was conducted, as well as grey literature databases, from inception to June 2017. Two authors independently selected studies, extracted data and appraised methodological quality. If heterogeneous, data were analysed descriptively. Where studies were homogeneous, data were pooled through a meta-analysis. Results: 23 studies were included. Annual prevalence for patellofemoral pain in the general population was reported as 22.7%, and adolescents as 28.9%. Incidence rates in military recruits ranged from 9.7 – 571.4/1,000 person-years, amateur runners in the general population at 1080.5/1,000 person-years and adolescents amateur athletes 5.1% - 14.9% over 1 season. One study reported point prevalence within military populations as 13.5%. The pooled estimate for point prevalence in adolescents was 7.2% (95% Confidence Interval: 6.3% - 8.3%), and in female only adolescent athletes was 22.7% (95% Confidence Interval 17.4% - 28.0%). Conclusion: This review demonstrates high incidence and prevalence levels for patellofemoral pain. Within the context of this, and poor long term prognosis and high disability levels, PFP should be an urgent research priority

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

The Present and Future Role of Insect-Resistant Genetically Modified Maize in IPM

Commercial, genetically-modified (GM) maize was first planted in the United States (USA, 1996) and Canada (1997) but now is grown in 13 countries on a total of over 35 million hectares (\u3e24% of area worldwide). The first GM maize plants produced a Cry protein derived from the soil bacteriumBacillus thuringiensis (Bt), which made them resistant to European corn borer and other lepidopteran maize pests. New GM maize hybrids not only have resistance to lepidopteran pests but some have resistance to coleopteran pests and tolerance to specific herbicides. Growers are attracted to the Btmaize hybrids for their convenience and because of yield protection, reduced need for chemical insecticides, and improved grain quality. Yet, most growers worldwide still rely on traditional integrated pest management (IPM) methods to control maize pests. They must weigh the appeal of buying insect protection “in the bag” against questions regarding economics, environmental safety, and insect resistance management (IRM). Traditional management of maize insects and the opportunities and challenges presented by GM maize are considered as they relate to current and future insect-resistant products. Four countries, two that currently have commercialize Bt maize (USA and Spain) and two that do not (China and Kenya), are highlighted. As with other insect management tactics (e.g., insecticide use or tillage), GM maize should not be considered inherently compatible or incompatible with IPM. Rather, the effect of GM insect-resistance on maize IPM likely depends on how the technology is developed and used

Dr. Buzby’s ToeGrips® Application Results in Minimal Changes in Kinetic Gait Parameters in Normal Dogs

Poor traction on slick surfaces is difficult for dogs with neurologic deficits, osteoarthritis, or recovering from injury or surgery. Many dogs respond inappropriately to slick surfaces by decreasing digital pad-floor contact and extending their toenails. A device marketed to increase paw-floor friction in dogs was evaluated. Fifteen normal dogs underwent kinetic gait analysis before and after application of Dr. Buzby’s ToeGrips®. Ground reaction forces, including vertical peak force (VPF) and impulse for each limb, were measured and compared between pre- and post-application values. Stance time was significantly increased in all limbs after toe grip application. Stride velocity was slower in all limbs but significantly slower only in the left forelimb. VPF was significantly deceased in both hindlimbs after toe grip application, but the decrease was within the group SDs. Vertical impulse was significantly increased in both forelimbs and in the right hindlimb. Dr. Buzby’s ToeGrips® result in a slower gait, with slightly decreased VPF in the hindlimbs and increased effort for propulsion kinetic changes were of minor magnitude and unlikely to be clinically relevant

Risk factors for short-term postoperative complications in the 8 weeks after tibial plateau leveling osteotomy in dogs weighing less than 15 kilograms: A retrospective study.

The purpose of this retrospective study was to evaluate the risk factors for short-term postoperative complications in the 8 weeks after unilateral tibial plateau leveling osteotomy (TPLO) for cranial cruciate ligament rupture in small dogs weighing less than 15 kg. Medical records were retrospectively reviewed for 90 dogs weighing 15kg. In this study, patients in which 2.4-mm TPLO plates were used were more likely to develop postoperative complications. Dogs weighing <15 kg that underwent TPLO had good short-term outcomes with minimal complications. In our study, the overall complication rate after TPLO in dogs weighing <15 kg is less than that historically reported in heavier dogs. Our data suggests that TPLO is a safe treatment option in small dogs with cranial cruciate ligament rupture

Fortetropin inhibits disuse muscle atrophy in dogs after tibial plateau leveling osteotomy.

OBJECTIVE:To determine if a commercial myostatin reducer (Fortetropin®) would inhibit disuse muscle atrophy in dogs after a tibial plateau leveling osteotomy. DESIGN:A prospective randomized, double-blinded, placebo-controlled clinical trial. ANIMALS:One hundred client-owned dogs presenting for surgical correction of cranial cruciate ligament rupture by tibial plateau leveling osteotomy. PROCEDURES:Patients were randomly assigned into the Fortetropin® or placebo group and clients were instructed to add the assigned supplement to the dog's normal diet once daily for twelve weeks. Enrolled patients had ultrasound measurements of muscle thickness, tape measure measurements of thigh circumference, serum myostatin level assays, and static stance analysis evaluated at weeks 0, 8, and 12. RESULTS:From week 0 to week 8, there was no change for thigh circumference in the Fortetropin® group for the affected limb (-0.54cm, P = 0.31), but a significant decrease in thigh circumference for the placebo group (-1.21cm, P = 0.03). There was no significant change in serum myostatin levels of dogs in the Fortetropin® group at any time point (P>0.05), while there was a significant rise of serum myostatin levels of dogs in placebo group during the period of forced exercise restriction (week 0 to week 8; +2,892 pg/ml, P = 0.02). The percent of body weight supported by the affected limb increased in dogs treated with Fortetropin® (+7.0%, P<0.01) and the placebo group (+4.9%, P<0.01) at the end of the period of forced exercise restriction. The difference in weight bearing between the Fortetropin® and placebo groups was not statistically significant (P = 0.10). CONCLUSION:Dogs receiving Fortetropin® had a similar increase in stance force on the affected limb, no significant increase in serum myostatin levels, and no significant reduction in thigh circumference at the end of the period of forced exercise restriction compared to the placebo. These findings support the feeding of Fortetropin® to prevent disuse muscle atrophy in canine patients undergoing a tibial plateau leveling osteotomy