Influence of the germline sequence on the thermodynamic stability and fibrillogenicity of human lambda 6 light chains

Light chain-associated amyloidosis is a fatal disease characterized by the aggregation and pathologic deposition of monoclonal light chain-related fragments as amyloid fibrils in organs or tissues throughout the body. Notably, it has been observed that proteins encoded by the lambda variable light chain (V(L)) gene segment 6a are invariably associated with amyloid deposition; however, the contribution of the gene to this phenomenon has not been established. In this regard, we have determined the thermodynamic stability and kinetics of in vitro fibrillogenesis of a recombinant (r) V(L) protein, designated 6aJL2, which contains the predicted sequences encoded by the 6a and JL2 germline genes. Additionally, we studied a 6a mutant (6aJL2-Arg25Gly), that is present in approximately 25% of all amyloid-associated lambda6 light chains. Remarkably, the wild-type 6aJL2 protein was more stable than were all known amyloidogenic kappa and lambda light chains for which stability parameters are available; more importantly, it was even more so (and less fibrillogenic) than the only clinically proven nonamyloidogenic lambda6 protein, Jto. Conversely, the mutated 6aJL2-R25G molecule was considerably less stable and more fibrillogenic than was the native 6aJL2. Our data indicate that the propensity of lambda6 light chains to form amyloid can not be attributed to thermodynamic instability of the germline-encoded Vlambda6 domain, but rather, is dependent on sequence alterations that render such proteins amyloidogenic.     

Adaptation to flooding in upland and lowland ecotypes of Cyperus rotundus, a troublesome sedge weed of rice: tuber morphology and carbohydrate metabolism

Background and aims

In recent years, Cyperus rotundus has become a problem weed in lowland rice (Oryza sativa) grown in rotation with vegetables in the Philippines. As the growth of C. rotundus is commonly suppressed by prolonged flooding, the ability of the weed to grow vigorously in flooded as well as upland conditions suggests that adapted ecotypes occur in these rotations. Studies were conducted to elucidate the mechanisms that permit C. rotundus to tolerate flooded soil conditions.

Methods

Upland and lowland ecotypes of C. rotundus were compared in terms of growth habit, carbohydrate reserves and metabolism, and activities of enzymes involved in alcoholic fermentation – alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC).

Key Results

The lowland ecotype has much larger tubers than the upland ecotype. Prior to germination, the amylase activity and total non-structural carbohydrate content in the form of soluble sugars were greater in the tubers of lowland plants than in those of upland C. rotundus. At 24 h after germination in hypoxic conditions, PDC and ADH activities in the lowland plants increased, before decreasing at 48 h following germination. In contrast, ADH and PDC activities in the upland plants increased from 24 to 48 h after germination.

Conclusions

Tolerance of lowland C. rotundus of flooding may be attributed to large carbohydrate content and amylase activity, and the ability to maintain high levels of soluble sugars in the tubers during germination and early growth. This is coupled with the modulation of ADH and PDC activities during germination, possibly to control the use of carbohydrate reserves and sustain substrate supply in order to avoid starvation and death of seedlings with prolonged flooding.Key words: Anoxia, ethanol fermentation, flooding tolerance, nutsedge, Cyperus rotundus, Pasteur effect, weed ecology     

Piezoelectric biosensors assisted with electroacoustic impedance spectroscopy: a tool for accurate quantitative molecular recognition analysis

In this work, electroacoustic impedance analysis based on a modified Butterworth-Van Dyke (BVD) model is used to complement resonance frequency measurements of piezoelectric crystal sensors for the identification and removal of interfering signals. This approach enables the accurate use of the Sauerbrey correlation to establish a direct relationship between mass deposited at the sensor surface and measured frequency variations. Kinetic models can thus be evaluated and binding constants estimated directly from the measured data. We further demonstrate the usefulness of this approach by applying it to the study of the formation of 11-hydroxy-1-undecanothiol self-assembled monolayers (SAM) as well as to the binding of streptavidin to immobilized biotin. Kinetic and equilibrium parameters were estimated from transient analysis, adsorption isotherms, Scatchard and Hill plots obtained from the frequency data for both the alkanethiol and streptavidin films. This strategy based on electroacoustic impedance assisted quartz-crystal microbalance (QCM) biosensors is expected to be a major contribution for the use of these piezoelectric devices as a reliable and cheap detection system that can easily be integrated into analytical techniques.     

Neurocysticercosis,a Persisting Health Problem in Mexico

Background

The ongoing epidemiological transition in Mexico minimizes the relative impact of neurocysticercosis (NC) on public health. However, hard data on the disease frequency are not available.

Methodology

All clinical records from patients admitted in the Instituto Nacional de Neurologia y Neurocirugia (INNN) at Mexico City in 1994 and 2004 were revised. The frequencies of hospitalized NC patients in neurology, neurosurgery and psychiatry services, as well as NC mortality from 1995 through 2009, were retrieved. Statistical analyses were made to evaluate possible significant differences in frequencies of NC patients'' admission between 1994 and 2004, and in yearly frequencies of NC patients'' hospitalization and death between 1995 and 2009.

Principal Findings

NC frequency in INNN is not significantly different in 1994 and 2004. Between these two years, clinical severity of the cases diminished and the proportion of patients living in Mexico City increased. Yearly frequencies of hospitalization in neurology and psychiatry services were stable, while frequencies of hospitalization in neurosurgery service and mortality significantly decreased between 1995 and 2009.

Conclusions

Our findings show a stable tendency of hospital cases during the last decade that should encourage to redouble efforts to control this ancient disease.     

Comparative anatomy of the stem,leaf and inflorescence basal axis of Polianthes L. (Asparagaceae,Agavoideae) species

The genus Polianthes belongs to Asparagaceae, subfamily Agavoideae (APG III, 2009) and is endemic to Mexico, spanning the states of Chihuahua and Tamaulipas in the north, and extending to the state of Oaxaca in the south. Its species are perennial, herbaceous plants with corms and bulbs. Their leaves are green or glaucous, linear or lanceolate. Inflorescences are in racemes or spikes with narrow and widely infundibuliform flowers, varying in color from white to red. The fruit is a capsule with black seeds. The number of species of Polianthes varies depending on the criteria to classify them. For example, in the first revision for the genus, Rose (1903) recognized 12 species. According to Espejo and López (1992), the genus has 15 species, whereas GarcíaMendoza and Galván (1995) reported 12 species, and Solano and Feria (2007) recognized 14 species and three varieties. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

FEV1 inversely correlates with metalloproteinases 1, 7, 9 and CRP in COPD by biomass smoke exposure

Background

Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis. The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).

Methods

Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).

Results

Plasma levels of MMP-1, MMP-7, MMP-9, and MMP-9/TIMP-1 and CRP were higher in BE and TS than in the NS healthy women (p <0.01). An inverse correlation between MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP plasma concentrations and FEV₁ was observed.

Conclusions

Increase of MMPs and CRP plasma concentrations in BE suggests a systemic inflammatory phenomenon similar to that observed in COPD associated to tobacco smoking, which may also play a role in COPD pathogenesis.     

Prenatal and Postnatal Exposure to DDT by Breast Milk Analysis in Canary Islands

Introduction

The use of p,p′-dichlorodiphenyltrichloroethane (DDT) has been banned since the late 1970s due to its toxicity. However, its long half-life makes it persistent in the environment and, consequently, almost everyone has DDT residues in the body. Human milk constitutes an ideal non-conventional matrix to investigate environmental chronic exposure to organochlorine compounds (OCs) residues. The study aimed to identify potential population risk factors of exposure to DDT due to the proximity to countries where it is still used.

Methods

Seventy-two consecutive lactating women were prospectively included in Tenerife, Canary Islands (Spain). A validated questionnaire was used to obtain socioeconomic, demographics data, and daily habits during pregnancy. DDT levels in breast milk were measured by gas chromatography with-electron capture detector (GC-ECD). Anthropometrics measurements in newborns were obtained.

Results

Thirty-four out of 72 (47.2%) of the analysed milk samples presented detectable levels of DDT (mean: 0.92 ng/g), ranging between 0.08 to 16.96 ng/g. The socio-demographic variables did not significantly differ between detectable DDT and non-detectable DDT groups. We found positive association between DDT levels and vegetables (OR (95%CI): 1.23 (1.01–1.50)) and poultry meat (OR (95%CI): 2.05 (1.16–3.60)) consumption, and also between the presence of DDT in breast milk and gestational age (OR (95%CI): 0.59 (0.40–0.90)).

Conclusions

DDT is present in breast milk of women at the time of delivery. Residual levels and the spread from countries still using DDT explain DDT detection from vegetables and from animal origin food. The presence of this compound in breast milk represents a pre- and postnatal exposure hazard for foetuses and infants due to chronic bioaccumulation and poor elimination, with possible deleterious effects on health. This data should be used to raise awareness of the risks of OCs exposure and to help establish health policies in order to avoid its use worldwide and thus, to prevent its propagation.     

Circadian Locomotor Activity Under Artificial Light in the Freshwater Crab Pseudothelphusa americana

Long-term recordings of locomotor activity were obtained from intact freshwater crabs, Pseudothelphusa americana in constant darkness (DD), constant light (LL) and different light-dark (LD) protocols. Bimodal rhythms were typically observed in this crab when subjected to DD or LD, with bouts of activity anticipating lights-on and lights-off, respectively. Freerunning circadian rhythms were expressed in both DD and LL for longer than 30 days. In DD, we observed that some animals presented different period lengths for each activity component. During LL, activity was primarily unimodal, however spontaneous splitting of the rhythms were observed in some animals. When activity was recorded under artificial long days, the morning bouts maintained their phase relationship but the evening bouts changed their phase relationship with the Zeitgeber. Our results indicate that, bimodal locomotor activity rhythm in the crab Pseudothelphusa americana is variable among organisms. The characteristics of phase relationship with LD and responses to LL for morning and evening bouts, suggest that, locomotor activity could be driven by multiple oscillators, and that coupling between these oscillators may be regulated by light.     

Life history varies with migratory distance in western sandpipers Calidris mauri

The propensity of migratory waders to remain on the non-breeding grounds during the arctic breeding season ("oversummer") in their first biological year of life ("juveniles") may be latitude, and thus migratory distance dependent. We compared the extent of preparation for northward migration of western sandpipers Calidris mauri spending the non-breeding season in México and Panamá during 1995–1998. During winter residency and premigratory periods, we measured body mass and scored the extent of dull basic versus bright alternate breeding plumage of captured juveniles and adults (second biological year or older), and obtained additional plumage scores from observations of uniquely colour banded birds. Nearly all western sandpipers in México prepared for northward migration by increasing body mass and moulting into breeding plumage. In Panamá, most adults prepared for migration, but few, if any, juveniles did so. Patterns of body mass and breeding plumage development do not generally support the hypothesis that oversummering by juveniles results directly from less efficient foraging or from resource competition with adults. We suggest instead that costs directly associated with migratory distance per se influence the life history strategies of sandpipers spending the non-breeding seasons at different latitudes. This latitudinal difference should interact with the well documented sex-ratio cline in non-breeding distribution (male western sandpipers predominating in northern parts of the range and females in southern parts). This suggests that females have more conservative life histories, prioritizing first year survivorship, relative to males that instead weight first-year breeding opportunities.