Paracoccidioidomycosis in people living with HIV/AIDS: A historical retrospective cohort study in a national reference center for infectious diseases,Rio de Janeiro,Brazil

Paracoccidioidomycosis (PCM) is one of the main endemic systemic mycoses in Latin America, usually occurring in rural areas. When PCM occurs simultaneously with underlying immunosuppressive conditions, it can present as an opportunistic disease. Between 2000 and 2017, literature reported around 200 PCM cases in people living with HIV/AIDS (PLWHA). To address research gaps on this co-infection and to study its possible temporal changes in the last decade, we performed an active co-infection case search on the HIV/AIDS and PCM cohorts from a Brazilian reference center database from 1989 to 2019. We found 20 PLWHA among 684 PCM patients (2.92%), predominantly male (70.0%) and urban workers (80.0%). The median age of patients was higher in the 2010–2019 decade (p = 0.006). The occurrence of PCM in PLWHA was lower when compared with other fungal diseases. Although 50.0% of the patients had already been diagnosed with HIV infection and presented CD4+ T cell counts greater than 200/mm³ at the time of PCM diagnosis, the suspicion of immunosuppression in the context of atypical and more severe clinical forms of PCM revealed the diagnosis of HIV infection in 35.0% of the patients. Two (10.0%) patients had an evolution compatible with immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART).We highlight the importance of considering a PCM diagnosis in PLWHA to prevent a late-onset treatment and progression to severe manifestations and unfavorable outcomes. In addition, HIV investigation is recommended in PCM patients, especially those with atypical and more severe clinical presentations.     

BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH)

The array CGH technique (Array Comparative Genome Hybridization) has been developed to detect chromosomal copy number changes on a genome-wide and/or high-resolution scale. It is used in human genetics and oncology, with great promise for clinical application. Until recently primarily PCR amplified bacterial artificial chromosomes (BACs) or cDNAs have been spotted as elements on the array. The large-scale DNA isolations or PCR amplifications of the large-insert clones necessary for manufacturing the arrays are elaborate and time-consuming. Lack of a high-resolution highly sensitive (commercial) alternative has undoubtedly hindered the implementation of array CGH in research and diagnostics. Recently, synthetic oligonucleotides as arrayed elements have been introduced as an alternative substrate for array CGH, both by academic institutions as well as by commercial providers. Oligonucleotide libraries or ready-made arrays can be bought off-the-shelf saving considerable time and efforts. For RNA expression profiling, we have seen a gradual transition from in-house printed cDNA-based expression arrays to oligonucleotide arrays and we expect a similar transition for array CGH. This review compares the different platforms and will attempt to shine a light on the ‘BAC to the future’ of the array CGH technique.     

The green thorns of Ulex europaeus play both defensive and photosynthetic roles: consequences for predictions of the enemy release hypothesis

Biological Invasions - The widespread invasive success of Ulex europaeus, a thorny shrub native to NW Europe, remains to be understood from a functional perspective. According to the Enemy Release...     

Role of Zinc in Zinc-α2-Glycoprotein Metabolism in Obesity: a Review of Literature

Biological Trace Element Research - Excessive adipose tissue promotes the manifestation of endocrine disorders such as reduction of the secretion of zinc-α2-glycoprotein (ZAG), an adipokine...     

The Response to Stimulation in Neurons and Astrocytes

Neurochemical Research - The brain uses mainly glucose as fuel with an index of glucose to oxygen utilization close to 6, the maximal index if all glucose was completely oxidized. However, this...     

Cerebroid Ganglion is the Presumptive Pacemaker of the Circadian Rhythm of Electrical Response to Light in the Crayfish

One of the most widely studied circadian rhythms in invertebrates is that of light responsiveness whose underlying mechanisms seem to involve different groups of oscillators which act as pacemakers. Although, in crayfish, there are clear circadian rhythms in the electroretinogram (ERG) amplitude, the precise location of the pacemaker system driving this rhythm is uncertain. Some data suggest that the circadian pacemaker could be located in a group of neurosecretory cells of the supraesophageal ganglion (the cerebroid ganglion or brain) and that the sinus gland plays a determinant role in the generation and expression of this rhythm through periodic release of pigment-dispersing hormone (PDH). The aim of this work is to examine the role of the brain in the expression of the ERG circadian activity. The hypothesis we test is that the electrical activity at the brain level has a circadian behavior in the firing pattern of spontaneous multiunit activity (MUA) and in visual evoked potentials (VEPs). The results indicate that there are robust circadian rhythms in both MUA, recorded from several regions of the brain, and in the averaged VEPs recorded from the protocerebrum area. These rhythms are 180° out of phase to one another. The rhythm of VEPs showed a main peak at midnight which was in close phase relationship with the ERG amplitude rhythm.     

Optimal mass selection policies for schemes with overlapping generations and restricted inbreeding

Optimum breeding schemes for maximising the rate of genetic progress with a restriction on the rate of inbreeding (per year or per generation) are investigated for populations with overlapping generations undergoing mass selection. The optimisation is for the numbers of males and females to be selected and for their distribution over age classes. Expected rates of genetic progress (ΔG) are combined with expected rates of inbreeding (ΔF) in a linear objective function (Φ = ΔG - λΔF) which is maximised. A simulated annealing algorithm is used to obtain the solutions. The restriction on inbreeding is achieved by increasing the number of parents and, in small schemes with severe restrictions, by increasing the generation interval. In the latter case the optimum strategy for obtaining the maximum genetic gain is far from truncation selection across age classes. In most situations, the optimum mating ratio is one but the differences in genetic gain obtained with different mating ratios are small. Optimisation of schemes when restricting the rate of inbreeding per generation leads to shorter generation intervals than optimisation when restricting the rate of inbreeding per year.     

Tuning of the FMN binding and oxido-reduction properties by neighboring side chains in Anabaena flavodoxin

Contribution of three regions (phosphate-binding, 50’s and 90’s loops) of Anabaena apoflavodoxin to FMN binding and reduction potential was studied. Thr12 and Glu16 did not influence FMN redox properties, but Thr12 played a role in FMN binding. Replacement of Trp57 with Glu, Lys or Arg moderately shifted E_ox/sq and E_sq/hq and altered the energetic of the FMN redox states binding profile. Our data indicate that the side chain of position 57 does not modulate E_ox/sq by aromatic stacking or solvent exclusion, but rather by influencing the relative strength of the H-bond between the N(5) of the flavin and the Asn58-Ile59 bond. A correlation was observed between the isoalloxazine increase in solvent accessibility and less negative E_sq/hq. Moreover, E_sq/hq became less negative as positively charged residues were added near to the isoalloxazine. Ile59 and Ile92 were simultaneously mutated to Ala or Glu. These mutations impaired FMN binding, while shifting E_sq/hq to less negative values and E_ox/sq to more negative. These effects are discussed on the bases of the X-ray structures of some of the Fld mutants, suggesting that in Anabaena Fld the structural control of both electron transfer steps is much more subtle than in other Flds.