Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of NKX2-5 in blood vessels

NKX2-5 is a transcription factor required for the formation of the heart and vessels during development. Postnatal expression is significantly downregulated, and then re-activated in diseased conditions characterised by vascular remodelling. However, the mechanisms regulating NKX2-5 activation in diseased vessels remain unknown. The aim of this thesis is to identify these mechanisms and provide information on how the gene contributes to cardiovascular pathologies, such as sclerodermaassociated pulmonary hypertension. A case-control genetic association study was performed in two independent cohorts of scleroderma patients. Associated SNPs located in the NKX2-5 genomic region were cloned into reporter vectors, and transcriptional activity was assessed by reporter-gene assays. Associated SNPs were further evaluated through proteinDNA binding assays, chromatin immunoprecipitation and RNA silencing. Signalling mechanisms activating NKX2-5 expression were investigated in vascular endothelial and smooth muscle cells using a panel of selective inhibitors. Meta-analysis across the two independent cohorts revealed that rs3131917 was associated with scleroderma. Rs3132139, downstream of NKX2-5, was significantly associated with pulmonary hypertension in both cohorts. The region containing rs3132139 and rs3131917 was shown to be a novel functional enhancer, which increased NKX2-5 transcriptional activity through the binding of GATA6, c-JUN, and MEF-2c. An activator TEAD/YAP1 complex was shown to bind at rs3095870, another functional SNP upstream of NKX2-5 transcription start site, which showed marginal association with scleroderma. Signalling mechanisms, involving TGF-β, ERK5, AKT and hypoxia, stimulated NKX2-5 expression during phenotypic modulation of vascular endothelial and smooth muscle cells. Overall, the data showed that NKX2-5 is genetically associated with scleroderma and pulmonary hypertension. Functional evidence revealed a regulatory mechanism, activated by TGF-β, which results in NKX2-5 transcription in human vascular smooth muscle cells through the interaction of an upstream promoter and a novel downstream enhancer. These regulatory mechanisms can act as a model for NKX2-5 activation in cardiovascular disease characterised by vascular remodelling
Rare Intronic Variations in TP73 Gene Found in Patients with Alzheimer’s Disease

ABSTRACT TP73 gene encodes p73 transcription factor, crucial for neurogenesis and neuronal health maintenance. In aging brain, p73 haploinsufficiency increases deposition of tau aggregates, hallmark pathology of Alzheimer’s disease. Thus, TP73 gene can be an important candidate for studying Alzheimer’s disease susceptibility. To explore the role of nucleotide variations in regulatory region of TP73 on Alzheimer’s disease, the region encompassing exon 2 of 80 Alzheimer’s patients and 123 age-matched controls was sequenced. Prediction of functional impact of found variations were done by software like ‘SpliceAid’, ‘mutation t@sting’ and ‘RegRNA2.0’. Two rare variations rs5031052 (NG_017035.2: g.34771C>T) and rs141679680 (NG_017035.2:g.34875G>A) were found in Alzheimer’s patients in only heterozygous condition with minor allelic frequencies 0.01875 and 0.0125 respectively, significantly higher than global MAF count (p value of z test 0.04 and 0.01 respectively), but totally absent in the control group. In silico analysis reveals the importance of these variations in splicing and microRNA binding. These variations not only introduce intronic spicing enhancer motif but also modulate splicing factor recruitment. Moreover, they regulate microRNA binding by creating or destroying miRNA binding site. Thus, the researchers report, for the first time that these two rare variations may involve in manifestation of Alzheimer’s disease in our cohort.
A preliminary analysis of the association between perceived stigma and HIV-related pain

Objective HIV stigma remains common and has been associated with severity of HIV-related symptoms. Associations between HIV stigma and HIV-related pain, one of the most common symptoms in HIV, have not been investigated however. Data from low back pain populations suggest that stigma associates with worse pain intensity and so we hypothesised that the same would be the case in HIV. In a small pilot study we assessed the association between HIV stigma and pain intensity in PLWH with chronic pain while controlling for depression, a well-established correlate of pain. Methods Mediation analysis was used to assess the effect of depression on the relationship between stigma and pain intensity in a cross-sectional cohort of 50 PLWH and chronic pain (pain most days of the week for > 3 months) recruited in Johannesburg, South Africa. All participants were assessed using: HIV/AIDS stigma instrument – PLWA (HASI-P), 11-point numerical pain rating scale, and the Beck Depression Inventory II. Results 88% (44/50) of participants reported experiencing some form of HIV stigma (HIV stigma scale score ≥ 1). Worst pain intensity and depressive symptoms individually correlated with total stigma score (Spearman’s r = 0.33, p = 0.02 for both). The mediation analysis highlighted that mediation of the relationship by depression was equivocal (b = −0.002, bootstrapped CI −0.02 to 0.00). Conclusions Whilst these preliminary data are marginal, they do suggest that associations between HIV stigma and HIV-related pain warrant further investigation. Future study should also include potential mechanisms, which may include mediation through depression.
Effects of salinity stress on some growth, physiological, biochemical parameters and nutrients in two pistachio (Pistacia vera L.) rootstocks

ABSTRACT In the present study, effects of salinity stress were evaluated in the leaves and roots of two pistachio cultivars (Badami-Rize-Zarand (BZ) and Badami-e-Sefid (BS)). In overall, salinity negatively affects growth of both cultivars with more pronounced effects on BS. The physiological reason of the reduction could be attributed to some extent to more depletion of photosynthetic pigment in BS. In both cultivars, salinity increased proline content. Moderate and high salinities increased the soluble sugar contents in BZ. In both cultivars, Na+ content increased in plant organs with increasing Na+ in the media. Salinity treatment decreased the Fe and Pi contents in BS cultivar, while they remained unchanged in BZ. These results show that BZ cultivar exhibits more tolerance to salinity stress than BS cultivar possibly by better growth performance, accumulating more osmolytes, lesser accumulation of toxic sodium ion and lower Na+/K+ in the shoots as well as maintaining nutrient contents.
New information on the Cenomanian bothremydid turtle Algorachelus based on new, well-preserved material from Spain

Abstract. Algorachelus peregrinus is the oldest representative of the crown group Pleurodira known in Laurasia. The type locality of this bothremydid is Algora, situated in central Spain, at levels deposited during the uppermost middle–lowermost upper Cenomanian. A new excavation was recently carried out in this town. As a result, abundant material of Algorachelus peregrinus has been found. Several complete shells, as well as numerous partial carapaces and plastra, are presented here. The abundance of remains allows the analysis of the general patterns by which some of the shells of this littoral form were partially or totally disarticulated. The analysis of these remains not only shows several pathologies but also improves the knowledge about the anatomy and intraspecific variability of Algorachelus peregrinus. This new information allows the revision of other Cenomanian forms of Bothremydidae, both from the Middle East and from North America. Thus, Algorachelus is identified in these regions, being represented in the early or middle Cenomanian of Palestine by the new combination Algorachelus parvus, and in the uppermost Cenomanian of Utah by the new combination Algorachelus tibert. Therefore, a relatively fast and widely distributed geographic dispersion event is recognized, corresponding to the oldest dispersal event so far identified for a lineage of Pleurodira from Gondwana to Laurasia.
Addition of Dried Blood Plasma to Feed of Minks During Lactation and Rearing of Kits

Abstract Studies on the effects of dried blood plasma on certain health parameters of mink (of the pastel variety) were conducted during lactation and the rearing of the kits. The study included two groups of mink (control group and experimental group). Animals in the experimental group received 0.5 % of dry blood plasma and the control group did not receive the plasma supplement. From the whole blood of both groups the direct and indirect haematological indices were recorded. Also, in both groups, the histopathological and immunohistochemical studies were performed on the: liver, kidneys, lymph nodes, spleen, and intestinal segments. From the experimental group some of the organs examined demonstrated slightly altered histopathology.
Multiple myeloma immunoglobulin λ translocations portend poor prognosis

Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed ‘high-risk’. To better understand and identify high-risk myeloma, we analyzed the translocation landscape of 826 newly-diagnosed patients by whole genome sequencing as part of the CoMMpass study. Translocations at the IgL locus were present in 10% of myeloma patients, and corresponded with poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, which is routinely diagnosed clinically whereas IgL-translocations are not. Thus, it is likely that the majority of IgL-translocated myeloma is being misclassified. The IgL enhancer is among the strongest in myeloma cells, indicating it can robustly drive oncogene expression when translocated. Consistent with this, IgL-translocated patients failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor Ikaros. These data implicate the IgL enhancer as resistant to IMiD-inhibition, and when translocated, as a driver of poor prognosis.
Effect of disturbance on litter dynamics in moist tropical forest of eastern Nepal

Litterfall is an important vector of nutrient and carbon recycling in forest ecosystems. Present study was conducted in moist tropical forest of eastern Nepal to understand the effect of disturbance on litter dynamics. Litterfall was estimated at monthly intervals from one litter trap (1 m × 1 m) at each of the 70 sampling plots while litter mass accumulated at each sampling plot was collected once every season from one 1 m × 1 m plot. The total annual litterfall in undisturbed forest (UF) was 11.8 Mg ha −1 yr −1 which decreased by 54.2% in disturbed forest (DF). Leaves accounted for 69% (UF) to 76% (DF) of total litterfall while non-leaf litter formed the rest. Seasonal pattern exhibited a concentrated litterfall in summer season during March to June when more than 70% litterfall occurred in both stands. Forest floor litter mass also decreased due to forest disturbance. The total input of nutrients to the soil through litterfall in UF was more than double as compared to DF. The nutrient stocks in litter mass were in the order: N > K > P in both stands. Key disturbance activities like lopping, litter removal, tree felling, grazing, fire etc. in the peripheral part of the forest should be strictly prohibited by imposing rules and regulations so that status of biodiversity would be restored. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License .
Computational models of the morphology of the developing neonatal human brain

Automated medical image analysis has made significant progress over the past decades. With recent advances in acquiring high quality in vivo images of the developing human brain, analysing this data for the purpose of understanding brain development is rapidly becoming feasible. Premature birth increases the risk of developing neurocognitive and neurobehavioural disorders. Studying the morphology and function of the brain during maturation, provides us not only with a better understanding of normal development, but may help identify causes for these. A difficulty is to differentiate between neurodevelopmental consequences and normal variation. Reference models are therefore needed. This thesis presents computational methods used to obtain such models. As a prerequisite, an efficient topology-preserving registration is required. Existing methods have been evaluated mostly on adult brain images, with considerably different shape and appearance. We evaluate approaches for the fast diffeomorphic registration on a publicly available neonatal brain image dataset, and present an improved inverse consistent variant of the stationary velocity free-form deformation algorithm. We employ this algorithm for the construction of a spatio-temporal atlas of the neonatal brain, and compare two different approaches. The first approach is based on the registration of all pairs of images. Residual misalignment thereby still impacts the sharpness of the atlas. More detail is preserved with an iterative refinement of the transformations relating each image to the atlas space. We developed a second approach, which jointly estimates mean shape and longitudinal change iteratively. The final atlas demonstrates increased sharpness and temporal consistency. Finally, we present deformable models for the reconstruction of the neonatal cortex, which correct for common errors observed in state-of-the-art neonatal brain segmentations. Our models were found by experts to be superior to the original segmentation in terms of accurately delineating the cortical anatomy, and form a vital component of image processing pipelines of the Developing Human Connectome Project.
Spatial distribution of juvenile fish species in nursery grounds of a tropical coastal area of the south-western Atlantic

Background. Assessing patterns in habitat utilization and changes in the composition of biont assemblages is a key tool for efficient ecosystem conservation planning and management. Nevertheless, habitat use patterns by juvenile fish still need more comprehension. Therefore, the presently reported study investigated relations between the type of nursery ground and the structure of juvenile fish assemblages in a tropical coastal area of the south-western Atlantic. Materials and methods. From December 2009 to November 2010, we conducted monthly sampling of ichthyofauna in two habitat types (mangrove and sandy beach) used as nursery grounds by juvenile fish of the south-western Atlantic. Species richness and abundance were used to identify spatial and temporal patterns in the distribution of fish assemblages throughout habitats’ dynamics. Results. A total of 845 fishes representing 16 families and 34 species were found during the presently reported study: Albula vulpes (Linnaeus, 1758); Atherinella brasiliensis (Quoy et Gaimard, 1825); Strongylura marina (Walbaum, 1792); Tylosurus acus acus (Lacepède, 1803); Caranx crysos (Mitchill, 1815); Caranx latus Agassiz, 1831; Oligoplites saurus (Bloch et Schneider, 1801); Selene setapinnis (Mitchill, 1815); Selene vomer (Linnaeus, 1758); Centropomus parallelus Poey, 1860; Centropomus undecimalis (Bloch, 1792); Harengula clupeola (Cuvier, 1829); Opisthonema oglinum (Lesueur, 1818); Anchoa tricolor (Spix et Agassiz, 1829); Anchovia clupeoides (Swainson, 1839); Diapterus auratus Ranzani, 1842; Diapterus rhombeus (Cuvier, 1829); Eucinostomus argenteus Baird et Girard, 1855; Eucinostomus gula (Quoy et Gaimard, 1824); Eucinostomus melanopterus (Bleeker, 1863); Bathygobius soporator (Valenciennes, 1837); Conodon nobilis (Linnaeus, 1758); Haemulon plumierii (Lacepède, 1801); Haemulopsis corvinaeformis (Steindachner, 1868); Hemiramphus brasiliensis (Linnaeus, 1758); Lutjanus apodus (Walbaum, 1792); Lutjanus griseus (Linnaeus, 1758); Lutjanus jocu (Bloch et Schneider, 1801); Mugil brevirostris (Ribeiro, 1915); Mugil curema Valenciennes, 1836; Mugil curvidens Valenciennes, 1836; Paralichthys tropicus Ginsburg, 1933; Sphyraena barracuda (Edwards, 1771); Sphoeroides testudineus (Linnaeus, 1758). No significant differences in species richness and total abundance were found between habitats and seasons. Nevertheless, our analyses showed that distinct sets of species use these areas. Moreover, we identified a strong relation between the rainfall and the species turnover in both habitats studied. Conclusion. Diversity of nursery grounds in coastal areas not only increases fish diversity but also plays an important role in the sustaining fish stocks.
Rapid multiplication of Withania somnifera using axillary leaf segments

An efficient micropropagation protocol has been developed for rapid micropropagation of Withania somnifera (L.) Dunal. Multiple shoots were induced by culturing axillary leaf explants excised from mature plants on Murashige and Skoog's basal medium supplemented with various combinations of BAP (N6 benzyle- aminopurine), Kn (Kinetin) & IAA (indole-3-acetic acid) formed direct shoot regeneration and indirect organogenesis through callus. The optimal level of BAP and IAA supplementation to the culture medium was 4.4 µM and 2.8 µM for 7 days to 10 days induction period followed by subculturing on Modified MS medium devoid of IAA produced maximum number of multiplication frequency (86%), mean number of shoots (20.5±0.4) and shoot length (1.6±0.3 cm) per explants. The regenerated shoots rooted best on half-strength MS medium supplemented with IBA 6.8 µM or NAA (α- naphthalene acetic acid) 7.5 µM. The micropropagated shoots with well developed roots were successfully established in pots containing a mixture of garden soil, sand and vermicompost (1:1:1 v/v) and grown in green house with 100% survival rate. The regenerated plants were morphologically uniform and exhibited similar growth characteristics and vegetative morphology to the donor plants.
Plant and fungal use in Tusheti, Khevsureti, and Pshavi, Sakartvelo (Republic of Georgia), Caucasus

In this study, we documented traditional plant use in Tusheti, Khevsureti, and Pshavi and hypothesized that (i) plant use knowledge in general would be higher in isolated high elevation communities, and that (ii) use of home gardens would be much more restricted to lower elevation settings. Fieldwork was conducted in Khevsureti, Pshavi, and Tusheti. Interviews using semi-structured questionnaires were conducted with 74 participants. In the present study, we encountered 317 plant species belonging to 203 genera of 80 families being used in the research region. Of these, 197 species were exclusively wild-harvested, 73 were grown in homegardens, and 47 were both grown in gardens and sourced in the wild. The ordinations in plant-space and in use-space were significantly fit by elevation of informant community, and community itself. Age and gender did not significantly fit the distribution of informants across either plant-space or use-space, respectively. Number of use-reports was highest across all communities in the food and medicinal use-categories, and informant consensus. Species with especially high use-diversity (UD) tended to be woody species although. Species with high use-value (UV) were mostly managed/domesticated species from home orchards, gardens, or farms. Plant species, and uses, found in our study, showed clear relations to the wider Eurasian cultural complex. The species number found was, however, far higher than in any published study from either the region or the wiser Mediterranean and Eurasia. The maintenance of home gardens in Georgia serves as socio-ecological memory. While the great variety of plant species used in the Georgian Caucasus might provide a reservoir for food security climate change is starting to affect both natural floristic diversity and gardens both in the Caucasus as well as continent wide.
Dietary zeolite clinoptilolite supplementation influences chemical composition of milk and udder health in dairy cows

Dražen ĐURIČIĆ, DVM, PhD, Assistant Professor, Veterinary Practice Đurđevac, Đurđevac, Croatia; Miroslav BENIĆ, DVM, PhD, Assistant Professor, Luka CVETNIĆ, DVM, Assistant, Croatian Veterinary Institute, Zagreb, Croatia; Nino MAĆEŠIĆ, DVM, PhD, Assistant Professor, Hrvoje VALPOTIĆ, DVM, PhD, Assistant Professor, Romana TURK, Mag. Med. Biochem. , PhD, Associate Professor, Vesna DOBRANIĆ, DVM, PhD, Associate Professor, Damjan GRAČNER, DVM, PhD, Full Professor, Silvijo VINCE, DVM, PhD, Assistant Professor, Juraj GRIZELJ, DVM, PhD, Associate Professor, Martina LOJKIĆ, DVM, PhD, Associate Professor, Marko SAMARDŽIJA*, DVM, PhD, Full Professor, (corresponding author, e-mail: smarko@vef.hr), Faculty of Veterinary Medicine University of Zagreb, Croatia; Jože STARIČ, DVM, PhD, Assistant Professor, Faculty of Veterinary Medicine University of Ljubljana, Slovenia Introduction
Biological relevance of streamflow metrics: regional and national perspectives

Protecting the health of streams and rivers requires identifying ecologically significant attributes of the natural flow regime. Streamflow regimes are routinely quantified using a plethora of hydrologic metrics (HMs), most of which have unknown relevance to biological communities. At regional and national scales, we evaluated which of 509 commonly used HMs were associated with biological indicators of fish and invertebrate community integrity. We quantified alteration of each HM by using statistical models to predict site-specific natural baseline values for each of 728 sites across the USA where streamflow monitoring data were available concurrent with assessments of invertebrate or fish community integrity. We then ranked HMs according to their individual association with biological integrity based on random forest models that included HMs and other relevant covariates, such as land cover and stream chemistry. HMs were generally the most important predictors of biological integrity relative to the covariates. At a national scale, the most influential HMs were measures of depleted high flows, homogenization of flows, and erratic flows. Unique combinations of biologically relevant HMs were apparent among regions. We discuss the implications of our findings to the challenge of selecting HMs for streamflow research and management.