Insulin-like Growth Factor I (IGF-I)-induced Chronic Gliosis and Retinal Stress Lead to Neurodegeneration in a Mouse Model of Retinopathy

Insulin-like growth factor I (IGF-I) exerts multiple effects on different retinal cell types in both physiological and pathological conditions. Despite the growth factor''s extensively described neuroprotective actions, transgenic mice with increased intraocular levels of IGF-I showed progressive impairment of electroretinographic amplitudes up to complete loss of response, with loss of photoreceptors and bipolar, ganglion, and amacrine neurons. Neurodegeneration was preceded by the overexpression of genes related to retinal stress, acute-phase response, and gliosis, suggesting that IGF-I altered normal retinal homeostasis. Indeed, gliosis and microgliosis were present from an early age in transgenic mice, before other alterations occurred, and were accompanied by signs of oxidative stress and impaired glutamate recycling. Older mice also showed overproduction of pro-inflammatory cytokines. Our results suggest that, when chronically increased, intraocular IGF-I is responsible for the induction of deleterious cellular processes that can lead to neurodegeneration, and they highlight the importance that this growth factor may have in the pathogenesis of conditions such as ischemic or diabetic retinopathy.     

Rapid Conformational Epitope Mapping of Anti-gp120 Antibodies with a Designed Mutant Panel Displayed on Yeast

gp120 is a substrate for protein engineering both for human immunodeficiency virus (HIV) immunogen design and as a bait for isolating anti-HIV antibodies from patient samples. In this work, we describe the display of a stripped core gp120 on the yeast cell surface. Validation against a panel of neutralizing antibodies confirms that yeast-displayed gp120 presents the CD4 binding site in the correct conformation. We map the epitope of the broadly neutralizing anti-gp120 antibody VRC01 using both a random mutagenesis library and a defined mutant panel and find that the resultant epitope maps are consistent with one another and with the crystallographically identified contact residues. Mapping the VRC01-competitive antibodies b12 and b13 reveals energetic differences in their epitopes that are not obvious from existing crystal structures. These data suggest mutation sets that abrogate binding to broadly neutralizing antibodies with greater specificity than the canonical mutation D368R, useful in rapidly assessing the nature of a vaccine response.     

Interactive effects of UV radiation and water availability on seedlings of six woody Mediterranean species

To assess the effects of UV radiation and its interaction with water availability on Mediterranean plants, we performed an experiment with seedlings of six Mediterranean species (three mesophytes vs three xerophytes) grown in a glasshouse from May to October under three UV conditions (without UV, with UVA and with UVA+UVB) and two irrigation levels (watered to saturation and low watered). Morphological, physiological and biochemical measures were taken. Exposure to UVA+UVB increased the overall leaf mass per area (LMA) and the leaf carotenoids/chlorophyll a + b ratio of plants in relation to plants grown without UV or with UVA, respectively. In contrast, we did not find a general effect of UV on the leaf content of phenols or UVB‐absorbing compounds of the studied species. Regarding plant growth, UV inhibited the above‐ground biomass production of well‐watered plants of Pistacia lentiscus. Conversely, under low irrigation, UVA tended to abolish the reduction in growth experienced by P. lentiscus plants growing in a UV‐free environment, in accordance with UVA‐enhanced apparent electron transport rate (ETR) values under drought in this species. UVA also induced an overall increase in root biomass when plants of the studied species were grown under a low water supply. In conclusion, while plant exposition to UVA favored root growth under water shortage, UVB addition only gave rise to photoprotective responses, such as the increase in LMA or in the leaf carotenoids/chlorophyll a + b ratio of plants. Species‐specific responses to UV were not related with the xerophytic or mesophytic character of the studied species.     

An ultrastructural study of the egg wall surrounding the miracidium of the digenean Brandesia turgida ( ) (Plagiorchiida: Pleurogenidae), with the description of a unique cocoon-like envelope

The intrauterine eggs of the pleurogenid trematode Brandesia turgida ( Brandes, 1888), exhibiting advanced stages of miracidial differentiation and fully formed, ciliated miracidia, were examined by means of transmission electron microscopy (TEM). Each embryonated egg is composed of a mature miracidium surrounded by a four-layered egg wall: (1) an outer, anucleate layer external to the eggshell, which forms a thick cocoon; (2) the operculate egg-shell; (3) a small remnant of the compact, granular cytoplasm of the outer embryonic envelope (sensu stricto); and (4) a relatively distinct cellular remnant of the inner embryonic envelope. Layers enveloping the egg apparently play an important role in the protection, metabolism and storage of nutritive reserves for the developing miracidium. The outer, anucleate layer, or cocoon, situated externally to the eggshell and composed of a transparent, electron-lucent substance with numerous dense, osmiophilic islands attached to its peripheral membrane, has never previously been seen in TEM studies of the eggs of parasitic platyhelminths. The origin, formation, functional ultrastructure and chemical composition of this peculiar layer remain enigmatic, although its function appears to be protective. The thick, electron-dense eggshell resembles that of other trematodes, exhibiting a characteristic fissure zone around the operculum. The very small, indistinct remnants of the outer embryonic envelope appear in the form of a very thin, compact, granular cytoplasm closely attached to the inner surface of the eggshell. Conversely, the inner embryonic envelope is frequently apparent at one or both poles of the developed egg as a syncytial envelope formed by the fusion of mesomeres. This envelope, even in eggs containing a fully formed miracidium, still has the features of a metabolically active layer with an energy storage capability. Lysosome-like structures observed in some eggs may be involved in the autolysis of the embryonic envelopes.     

The oldest human fossil in Europe,from Orce (Spain)

The Orce region has one of the best late Pliocene and early Pleistocene continental paleobiological records of Europe. It is situated in the northeastern sector of the intramontane Guadix-Baza Basin (Granada, Andalusia, southern Spain). Here we describe a new fossil hominin tooth from the site of Barranco León, dated between 1.02 and 1.73 Ma (millions of years ago) by Electron Spin Resonance (ESR), which, in combination with paleomagnetic and biochronologic data, is estimated to be close to 1.4 Ma. While the range of dates obtained from these various methods overlaps with those published for the Sima del Elefante hominin locality (1.2 Ma), the overwhelming majority of evidence points to an older age. Thus, at the moment, the Barranco León hominin is the oldest from Western Europe.     

Screening for the presence of FMR1 premutation alleles in women with fibromyalgia

Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, non-restorative sleep and cognitive difficulties that affects 2–4% of the general population. Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out. In attempt to gather more data we screened for the FMR1 CGG expansion 700 DNA samples from unrelated fibromyalgia patients. This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia. The observed frequency of FMR1 premutation carriers (3 of 700, 0.4%) is not significantly different from the estimated rate in the general female population (1/250–1/400) (P = 0.539, P = 0.716). Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms, neurocognitive alterations and neurovegetative impairments. With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients. On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended. However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status.     

Biochronology of the first hominid remains in Europe using the vole Mimomys savini: Fuente Nueva 3 and Barranco León D,Guadix-Baza Basin,south-eastern Spain

The sites of Barranco León D (BL-D) and Fuente Nueva 3 (FN-3) in the Guadix-Baza Basin (Granada, Spain), together with the site of Sima del Elefante in the Sierra de Atapuerca (Burgos, Spain), constitute one of the oldest records of the earliest hominid population in the European continent west of Dmanisi (Georgia, Lesser Caucasus). In the Guadix-Baza Basin, evidence of human occupation has been found to date in the form of lithic industry (Mode 1) and cut marks in large-mammal fossil remains (mainly of hippopotamuses and elephants), and recently a human tooth considered as the oldest in Europe has been discovered. Although in the case of Sima del Elefante there is unanimity among the scientific community regarding the chronology of the unit in which the hominid remains were found (Unit TE9c, 1.22 Ma), there is continuing debate on the chronology of the sites of the Guadix-Baza Basin (FN-3 and BL-D). This applies especially to BL-D, as the numerical datings published for this site have a very high error range (1.4 ± 0.38 Ma). In this paper, the chronology of these two sites is determined using as a marker the morphological and morphometric changes undergone by Mimomys savini in its first lower molar (m1) over the course of its evolutionary history. It has been possible to confirm that the oldest human presence in the Guadix-Baza Basin and at Sima del Elefante (Atapuerca) share a similar chronology, dated to between 1.1 and 1.4 Ma. Apparently, the oldest site with human remains in Europe is seen to be BL-D, dated to 1.26 ± 0.13 Ma, followed by Level TE9c, dated to 1.22 ± 0.16 Ma, and FN-3, dated to 1.20 ± 0.12 Ma.     

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.