FGF21 mediates the lipid metabolism response to amino acid starvation

Lipogenic gene expression in liver is repressed in mice upon leucine deprivation. The hormone fibroblast growth factor 21 (FGF21), which is critical to the adaptive metabolic response to starvation, is also induced under amino acid deprivation. Upon leucine deprivation, we found that FGF21 is needed to repress expression of lipogenic genes in liver and white adipose tissue, and stimulate phosphorylation of hormone-sensitive lipase in white adipose tissue. The increased expression of Ucp1 in brown adipose tissue under these circumstances is also impaired in FGF21-deficient mice. Our results demonstrate the important role of FGF21 in the regulation of lipid metabolism during amino acid starvation.     

A New Species of Water Beetle,Hydraena delvasi,from Colombia,South America (Coleoptera: Hydraenidae)

The aquatic beetle Hydraena delvasi sp. n. from Colombia, belonging to the family Hydraenidae, is described and illustrated as a new species. The types were collected by F. Collantes during a recent visit to Colombia.     

Transient inactivation of myostatin induces muscle hypertrophy and overcompensatory growth in zebrafish via inactivation of the SMAD signaling pathway

Myostatin (MSTN) is the main negative regulator of muscle growth and development in vertebrates. In fish, little is known about the molecular mechanisms behind how MSTN inactivation triggers skeletal muscle enhancement, particularly regarding the signaling pathways involved in this process. Moreover, there have not been reports on the biotechnological applications of MSTN and its signal transduction. In this context, zebrafish underwent compensatory growth using fasting and refeeding trials, and MSTN activity was inactivated with dominant negative LAPD76A recombinant proteins during the refeeding period, when a rapid, compensatory muscle growth was observed. Treated fish displayed an overcompensation of growth characterized by higher muscle hypertrophy and growth performance than constantly fed, control fish. Treatment with LAPD76A recombinant proteins triggered inactivation of the SMAD signaling pathway in skeletal muscle, the main signal transduction used by MSTN to achieve its biological actions. Therefore, transient inactivation of MSTN during the compensatory growth of zebrafish led to a decrease in the SMAD signaling pathway in muscle, triggering muscle hypertrophy and finally improving growth performance, thus, zebrafish achieved an overcompensation of growth. The present study shows an attractive strategy for improving muscle growth in a fish species by mixing a classical strategy, such as compensatory growth, and a biotechnological approach, such as the use of recombinant proteins for inhibiting the biological actions of MSTN. The mix of both strategies may represent a method that could be applied in order to improve growth in commercial fish of interest for aquaculture.     

Reproduction and growth of Aphanopus carbo and A. intermedius (Teleostei: Trichiuridae) in the northeastern Atlantic

Commercial fishery landings of the black scabbardfish, Aphanopus carbo, from the Madeira mid‐water drifting longline fleet (northeastern Atlantic) were studied for 2 years within a Portuguese government programme for fishing management. The process noted that 20% of the total catch corresponded to the intermediate scabbardfish, Aphanopus intermedius. Length‐frequency distribution, and age, growth and reproduction of both species were analysed and compared. The results revealed significant differences in age and growth in influencing the length‐frequency distributions. Intermediate scabbardfish attained the largest size (148 cm TL) and age (15 years). However, the two species had similar reproductive strategies. According to data published on A. carbo in this region, it is thought to be very likely that previous studies unintentionally mixed both species together in their analyses.     

The arylalkylamine-N-acetyltransferase (AANAT) acetylates dopamine in the digestive tract of goldfish: A role in intestinal motility

Melatonin has been found in the digestive tract of many vertebrates. However, the enzymatic activity of the arylalkylamine-N-acetyltransferase (AANAT) and the hydroxindole-O-methyltransferase (HIOMT), the last two enzymes of melatonin biosynthesis, have been only measured in rat liver. Therefore, the first objective of the present study is to investigate the functionality of these enzymes in the liver and gut of goldfish, analyzing its possible daily changes and comparing its catalytic properties with those from the retina isoforms. The daily rhythms with nocturnal acrophases in retinal AANAT and HIOMT activities support their role in melatonin biosynthesis. In foregut AANAT activity also show a daily rhythm while in liver and hindgut significant but not rhythmic levels of AANAT activity are found. HIOMT activity is not detected in any of these peripheral tissues suggesting an alternative role for AANAT besides melatonin synthesis. The failure to detect functional HIOMT activity in both, liver and gut, led us to investigate other physiological substrates for the AANAT, as dopamine, searching alternative roles for this enzyme in the goldfish gut. Dopamine competes with tryptamine and inhibits retinal, intestinal and hepatic N-acetyltryptamine production, suggesting that the active isoform in gut is AANAT1. Besides, gut and liver produces N-acetyldopamine in presence of acetyl coenzyme-A and dopamine. This production is not abolished by the presence of folic acid (arylamine N-acetyltransferase inhibitor) in any studied tissue, but a total inhibition occurs in the presence of CoA-S-N-acetyltryptamine (AANAT inhibitor) in liver. Therefore, AANAT1 seems to be an important enzyme in the regulation of dopamine and N-acetyldopamine content in liver. Finally, for the first time in fish we found that dopamine, but not N-acetyldopamine, regulates the gut motility, underlying the broad physiological role of AANAT in the gut.     

Influence of survivin (BIRC5) and caspase-9 (CASP9) functional polymorphisms in renal cell carcinoma development: a study in a southern European population

Renal cell carcinoma (RCC) is the most common cancer of the adult kidney and its incidence and mortality has increase in the last 20 years. The disruption of cellular death is one the mechanism involved in cancer development. This process is precise regulated by apoptotic and anti-apoptotic molecules. Survivin (BIRC5) is a member of the inhibitor of apoptosis protein family and has the ability to inhibit the activation of the pro-apoptotic caspase-9 (CASP9). Thus BIRC5 and CASP9 functional polymorphisms might modulate the apoptosis and consequently RCC development. Our purpose was to investigate the potential role of BIRC5?31G/C and CASP9+83C/T functional polymorphisms in the risk for the development of RCC and metastatic disease. We studied the BIRC5?31G/C and CASP9+83C/T functional polymorphisms by PCR–RFLP and allelic discrimination using the 7300 real-time polymerase chain reaction system, respectively, in 178 RCC patients and in 305 healthy individuals. Regarding the BIRC5?31G/C polymorphism, there is a trend to an overrepresentation of CC genotype in RCC group compared with normal controls (aOR, 1.94; P = 0.053). We observed, after gender stratification and age-adjustment, that BIRC5?31CC and CASP9+83CT/TT genotypes were associated with an increased risk for RCC development in the female group of our southern European study population (aOR = 3.85; P = 0.019; aOR = 2.98; P = 0.028; respectively). Concerning the waiting time for onset of metastatic disease, we observed that BIRC5?31CC homozygous developed metastasis 8 years earlier than the G carriers using a Cox proportional hazard model with gender as covariate (HR = 4.9, P = 0.038, P _bootstrap = 0.009). The Cox regression proportional hazard model was validated using bootstrap statistic with 1,000 samples of the same number of patients as the original dataset. Our results suggest that individual differences influence the susceptibility to RCC and tumor behavior. This genetic profile may help to define higher risk groups that would benefit from individualized chemoprevention strategies and therapies.     

E-cadherin and adherens-junctions stability in gastric carcinoma: Functional implications of glycosyltransferases involving N-glycan branching biosynthesis,N-acetylglucosaminyltransferases III and V

Background

E-cadherin is a cell–cell adhesion molecule and the dysfunction of which is a common feature of more than 70% of all invasive carcinomas, including gastric cancer. Mechanisms behind the loss of E-cadherin function in gastric carcinomas include mutations and silencing at either the DNA or RNA level. Nevertheless, in a high percentage of gastric carcinoma cases displaying E-cadherin dysfunction, the mechanism responsible for E-cadherin dysregulation is unknown. We have previously demonstrated the existence of a bi-directional cross-talk between E-cadherin and two major N-glycan processing enzymes, N-acetylglucosaminyltransferase-III or -V (GnT-III or GnT-V).

Methods

In the present study, we have characterized the functional implications of the N-glycans catalyzed by GnT-III and GnT-V on the regulation of E-cadherin biological functions and in the molecular assembly and stability of adherens-junctions in a gastric cancer model. The results were validated in human gastric carcinoma samples.

Results

We demonstrated that GnT-III induced a stabilizing effect on E-cadherin at the cell membrane by inducing a delay in the turnover rate of the protein, contributing for the formation of stable and functional adherens-junctions, and further preventing clathrin-dependent E-cadherin endocytosis. Conversely, GnT-V promotes the destabilization of E-cadherin, leading to its mislocalization and unstable adherens-junctions with impairment of cell–cell adhesion.

Conclusions

This supports the role of GnT-III on E-cadherin-mediated tumor suppression, and GnT-V on E-cadherin-mediated tumor invasion.

General significance

These results contribute to fill the gap of knowledge of those human carcinoma cases harboring E-cadherin dysfunction, opening new insights into the molecular mechanisms underlying E-cadherin regulation in gastric cancer with potential translational clinical applications.     

A new case of partial 14q31.3-qter trisomy due to maternal pericentric inversion

Chromosome 14 is often involved in chromosome rearrangements, although pericentric inversions are rare. Here we report a mother carrying a pericentric inversion of chromosome 14, and her daughter with recombinant chromosome characterized by a partial distal 14q trisomy. Principal clinical findings of the child include facial anomalies, microcephaly, developmental delay, hypotonia and cardiac malformation. Her final karyotype was 46,XX,rec(14)dup(14q)inv(14)(p12q31)mat[20], arr 14q31.3qter(85,427,839–106,356,482)x3. This report brings new data about clinical features of partial 14q trisomy and molecular analysis enables the visualization of genes involved in the segment duplicated.     

Control of Salmonella Enteritidis on food contact surfaces with bacteriophage PVP-SE2

Abstract

Salmonella is one of the worldwide leading foodborne pathogens responsible for illnesses and hospitalizations, and its capacity to form biofilms is one of its many virulence factors. This work evaluated (bacterio)phage control of adhered and biofilm cells of Salmonella Enteritidis on three different substrata at refrigerated and room temperatures, and also a preventive approach in poultry skin. PVP-SE2 phage was efficient in reducing both 24- and 48-h old Salmonella biofilms from polystyrene and stainless steel causing 2 to 5 log CFU cm^?2 reductions with a higher killing efficiency at room temperature. PVP-SE2 phage application on poultry skins reduced levels of Salmonella. Freezing phage-pretreated poultry skin samples had no influence on the viability of phage PVP-SE2 and their in vitro contamination with S. Enteritidis provided evidence that phages prevented their further growth. Although not all conditions favor phage treatment, this study endorses their use to prevent and control foodborne pathogen colonization of surfaces.