Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development.

In mice, the yolk sac appears to play a crucial role in nourishing the developing embryo, especially during embryonic days (E) 7;-10. Lipoprotein synthesis and secretion may be essential for this function: embryos lacking apolipoprotein (apo) B or microsomal triglyceride transfer protein (MTP), both of which participate in the assembly of triglyceride-rich lipoproteins, are apparently defective in their ability to export lipoproteins from yolk sac endoderm cells and die during mid-gestation. We therefore analyzed the embryonic expression of apoB, MTP, and alpha-tocopherol transfer protein (alpha-TTP), which have been associated with the assembly and secretion of apoB-containing lipoproteins in the adult liver, at different developmental time points. MTP expression or activity was found in the yolk sac and fetal liver, and low levels of activity were detected in E18.5 placentas. alpha-TTP mRNA and protein were detectable in the fetal liver, but not in the yolk sac or placenta. Ultrastructural analysis of yolk sac visceral endoderm cells demonstrated nascent VLDL within the luminal spaces of the rough endoplasmic reticulum and Golgi apparatus at E7.5 and E8.5. The particles were reduced in diameter at E13.5 and reduced in number at E18.5;-19.The data support the hypothesis that the yolk sac plays a vital role in providing lipids and lipid-soluble nutrients to embryos during the early phases (E7;-10) of mouse development. secretion in mouse yolk sac during embryonic development.     

Comparison of Resistance to Cotton Leaf Curl Disease (Multan/Burewala) in Gossypium hirsutum L. Varieties and Breeding Lines

Twenty‐four cotton varieties and advance breeding lines were evaluated for their resistance to cotton leaf curl disease (CLCuD; Multan/Burewala) under natural field and in glasshouse conditions for two consecutive years. Resistance was based on symptom expression and disease severity index. All the cotton genotypes exposed to the vector whitefly in the field and artificially infected by grafting manifested a high level of resistance against CLCuD (Multan) with the exception of genotype NIAB‐999 that was moderately resistant. All the test varieties/breeding lines were highly susceptible to CLCuD (Burewala) both in the field and the glasshouse. However, substantial differences were noted between genotypes for disease index under field conditions. Graft inoculation studies showed that all genotypes inoculated with CLCuD (Burewala) developed disease within 9–13 days whereas those graft‐inoculated with CLCuD (Multan) developed symptoms from 15 to 22 days after grafting. Severe reduction occurred in plant morphology, fibre and yield parameters of cotton variety NIAB‐111 following inoculation with CLCuD (Burewala) as compared with CLCuD (Multan).     

HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia.

Highly active anti-retroviral therapies, which incorporate HIV protease inhibitors, resolve many AIDS-defining illnesses. However, patients receiving protease inhibitors develop a marked lipodystrophy and hyperlipidemia. Using cultured human and rat hepatoma cells and primary hepatocytes from transgenic mice, we demonstrate that protease inhibitor treatment inhibits proteasomal degradation of nascent apolipoprotein B, the principal protein component of triglyceride and cholesterol-rich plasma lipoproteins. Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity. However, in the presence of oleic acid, which stimulates neutral-lipid biosynthesis, protease-inhibitor treatment increased secretion of apolipoprotein B-lipoproteins above controls. These findings suggest a molecular basis for protease-inhibitor-associated hyperlipidemia, a serious adverse effect of an otherwise efficacious treatment for HIV infection.     

Restoration of Rice Husk-Adsorbed Lipase Activity after Rehydration

Hydrolytic and esterifying activities of lipase from Candida cylindracea adsorbed on rice husks were lost by dehydration using molecular sieve pellets and P₂O₅which removed 90-97% of the water after 9 days. However, only the esterifying activity of the enzyme was restored by gradual water transfer via the organic phase to the dried enzyme either by direct water addition or by using salt hydrates as water donors.     

Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data

BackgroundLittle is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns.Methods and findingsThe MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme’s first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%–75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients’ length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes.ConclusionsGood treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.

Éimhín Ansbro and co-workers report on provision of care for non-communicable diseases in a humanitarian setting in Jordan.     

Chemical Synthesis of 4-Trifluoromethylumbelliferyl-α-d-N-acetylneuraminic Acid Glycoside and Its Use for the Fluorometric Detection of Poorly Expressed Natural and Recombinant Sialidases

When compared to bacterial or viral sialidases, eukaryotic sialidases are expressed at lower levels and frequently show poor specific activities. The identification and characterization of sialidases from eukaryotes have been slowed down due to the limited sensitivity of available sialidase substrates. Therefore, we chemically synthesized a fluorogenic compound, 4-trifluoromethylumbelliferyl-α-d-N-acetylneuraminic acid (CF₃MU-Neu5Ac), and tested its use as a substrate for eight different sialidases, including enzymes from viral, bacterial, and eukaryotic sources. Kinetic analysis revealed CF₃MU-Neu5Ac to be a very sensitive sialidase substrate. Furthermore, this substance proves to be perfectly suitable for thein vivoexamination of sialidases and for the detection of recombinant sialidase by means of expression cloning.     

Autosomal dominant spastic paraplegia with anticipation maps to a 4-cM interval on chromosome 2p21-p24 in a large German family

Autosomal dominant familial spastic paraplegias (AD-FSP) are a group of genetically heterogeneous diseases characterised by a progressive spasticity of the lower limbs. Three loci have already been identified by genetic linkage studies on chromosomes 2p, 14q and 15q. Here we present linkage data from a large German family displaying AD-FSP with anticipation which confirms the existence of the FSP2 locus on chromosome 2p. The recombination events observed in our family define the critical region for the FSP2 gene to be within a 4-cM interval, flanked by markers D2S400 and D2S367. Moreover, clinical data from our family show evidence of anticipation, a phenomenon caused by trinucleotide expansion in several other neurodegenerative diseases. Received: 6 April 1996 / Revised: 22 April 1996     

Current progress in Striga management

The Striga, particularly S. he rmonthica, problem has become a major threat to food security, exacerbating hunger and poverty in many African countries. A number of Striga control strategies have been proposed and tested during the past decade, however, further research efforts are still needed to provide sustainable and effective solutions to the Striga problem. In this paper, we provide an update on the recent progress and the approaches used in Striga management, and highlight emerging opportunities for developing new technologies to control this enigmatic parasite.

Advances

• The recently established Striga control technologies, such as push-pull, toothpick, and imidazolinone seed dressing have opened up new opportunities for smallholder farmers to overcome this parasite.
• The development of low-cost and efficient germination stimulants together with an application protocol for rain-fed agriculture has made the suicidal germination strategy a realistic approach.
• Molecular elucidation of strigolactone biosynthesis and perception has led to the development of new chemicals that disrupt the communication between Striga and its hosts.