Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular cytogenetic characterization of a subtle interstitial del(3)(p25.3p26.2) in a patient with deletion 3p syndrome.

Deletion 3p syndrome is associated with characteristic facial features, growth failure, and mental retardation. Typically, individuals with deletion 3p syndrome have terminal deletions that result in loss of material from 3p25 to 3pter. We present a child with a clinical phenotype consistent with deletion 3p syndrome (ptosis, microcephaly, growth retardation, and developmental delay) and a subtle interstitial deletion in the distal portion of the short arm of chromosome 3, del(3)(p25.3p26.2). Fluorescence in situ hybridization (FISH) studies using 3p subtelomeric probes confirmed the terminal region of chromosome 3 was present. Sequence tagged sites (STS)-linked BAC clones mapping to chromosomal region 3p25-p26 were used to characterize the interstitial deletion by FISH. The results indicate the deletion is within a region of approximately 4.5 Mb between STS markers D3S3630 and D3S1304. This interstitial deletion lies within all previously reported terminal deletions in deletion 3p syndrome individuals, and represents the smallest reported deletion associated with deletion 3p syndrome. Characterization of the deletion may help identify genes important to growth and development that contribute to the deletion 3p syndrome phenotype when present in a hemizygous state.
Factors contributing to adverse maternal outcomes in patients with HELLP syndrome

Abstract Objective: To determine the prognostic factors for adverse maternal outcomes in women with complete HELLP syndrome. Methods: A retrospective cohort study was carried out by searching the hospital data for the diagnosis of HELLP syndrome according to Tennessee classification from January 2007 to January 2014. Data included a total of 171 patients between January 2007 and January 2014. The data were collected from the hospital records including demographic data variables, presence of preeclampsia/chronic hypertension, gestational age at the time of diagnosis, and adverse maternal outcomes in terms of eclampsia, disseminated intravascular coagulopathy, acute renal failure (ARF), pulmonary edema, abruptio placentae placental abruption, pleural effusion, ascites, transfusion, and death were determined as adverse maternal outcomes. Independent prognostic factors for each complication with adverse maternal outcome were determined. Results: A total of 171 patients between January 2007 and January 2014 were included in the study. Clinical and laboratory parameters of 171 patients were analyzed. Risk factors for adverse maternal outcomes were as follows; aspartate amino transferase (AST) > 316 U/L, alanine aminotransferase (ALT) > 217 U/L, total bilirubin >2.0 mg/dL, lactate dehydrogenase (LDH) > 1290 U/L, blood urea nitrogen (BUN) > 44 mg/dL, and low platelets (<50,000/mm3). The risk of eclampsia increased 4.1 times and 3.4 times in the presence of LDH >1290 U/L and headache, respectively. Younger maternal age also increased the risk of eclampsia. Risk of ARF increased 15 times at the levels of bilirubin >2.0. Conclusions: Younger age, headache, bilirubin >2.0 mg/dL, LDH >1290 U/L, and low platelets (<50,000/mm3) were independent prognostic risk factors for predicting adverse maternal outcomes.
Effects of Saralasin on Arterial Compliance in Normotensive and Hypertensive Rats: Role of Endothelium

We used an experimental model of in situ isolated carotid arteries to clarify the participation of angiotensin II (Ang II) in the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). The effects of local incubation with saralasin ([Sar1,Thr8]Ang II, 10−6 M) on carotid compliance were compared with the effects of endothelium removal and with those of total abolition of vasomotor tone with potassium cyanide (0.1 mg/ml). Operating carotid compliance measured for pressure values close to the mean arterial pressure of each group was (mean±SD) 12.6 ± 2.9×10−3 μl/ mm Hg • mm vessel in WKY rats and 8-2±1.6×10−3 μ/mm Hg • mm vessel in SHRs (p< 0.001). Witb intact endothelium, local incubation with saralasin increased carotid compliance by 24% in WKY rats and 23% in SHRs relative to control values (p<0.05 and p<0.001, respectively). Endothelium removal induced significant increases in carotid compliance in WKY rats (17%, p<0.01) and in SHRs (33%, p<0.001). After endothelium removal, saralasin induced significant further carotid compliance increases in both strains (+18%, p<0.001, and +11%, p<0.01, in WKY rats and SHRs, respectively). After potassium cyanide poisoning, carotid compliance did not increase further relative to saralasin values in both strains with or without endothelium. These findings suggest that Ang II receptors play a major role in the control of the basal vasomotor tone of large arteries in both normotensive and hypertensive rats. Furthermore, the increase in carotid compliance induced by local incubation with saralasin and with angiotensin converting enzyme inhibitors could involve similar mechanisms on the smooth muscle angiotensin receptors.
Airway status in civilian maxillofacial gunshot injuries in Johannesburg, South Africa.

BACKGROUND Airway management of the maxillofacial gunshot injury constitutes a critical decision and an area that requires review in the context of civilian injuries. Most of our knowledge is extrapolated from military experience, which constitutes a different trauma patient group. This paper reports a retrospective survey of airway status in relation to maxillofacial gunshot injuries. The objective is to correlate clinical findings with treatment decisions. METHODS A survey was done of 11,622 archived maxillofacial surgery records (1987-1992) in the three academic hospitals in Johannesburg. RESULTS There were 211 maxillofacial gunshot injuries, for which 92 patient records had sufficient detail for inclusion in the analysis. The typical patient was a black male aged 20-29 years, shot with a low-velocity bullet of 0.38 calibre, admitted to hospital the day of the injury, operated on within 4 days, and discharged 4 days later. The airway was threatened in 20/92 cases at admission; 12/20 cases were treated with oro-or nasotracheal intubation, and 9/12 later had elective tracheostomies; 8/20 needed immediate surgical airways, 5 tracheostomies and 3 cricothyroldotomies (all later converted to tracheostomies). Three of thirty-seven patients with normal airways on admission later required emergency tracheostomy. CONCLUSIONS An abnormal airway was significantly more likely after a high-velocity injury, and when the tongue, floor of mouth, midline or bilateral facial skeletal bones were involved.
Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Trial registration Clincialtrials.gov, NCT01119521
Reconstruction of a rough surface profile with an iterative method based on a rigorous direct wave scattering model

We numerically demonstrate that an iterative inverse method based on a rigourous wave scattering model can be used to retrieve the profile of a rough interface from the complex scattering amplitude in far-field. The method of moments, that is a numerical resolution of the boundary integral equations, is chosen as direct model, so that large profiles, with tens of wavelength, can be reconstructed. The two polarization cases are addressed and finally combined. Sub-wavelength resolution is reached, especially when multiple scattering occurs.
HLS5, a Novel RBCC (Ring Finger, B Box, Coiled-coil) Family Member Isolated from a Hemopoietic Lineage Switch, Is a Candidate Tumor Suppressor*

Hemopoietic cells, apparently committed to one lineage, can be reprogrammed to display the phenotype of another lineage. The J2E erythroleukemic cell line has on rare occasions developed the features of monocytic cells. Subtractive hybridization was used in an attempt to identify genes that were up-regulated during this erythroid to myeloid transition. We report here on the isolation of hemopoietic lineage switch 5 (Hls5), a gene expressed by the monocytoid variant cells, but not the parental J2E cells. Hls5 is a novel member of the RBCC (Ring finger, B box, coiled-coil) family of genes, which includes Pml, Herf1, Tif-1α, and Rfp. Hls5 was expressed in a wide range of adult tissues; however, at different stages during embryogenesis, Hls5 was detected in the branchial arches, spinal cord, dorsal root ganglia, limb buds, and brain. The protein was present in cytoplasmic granules and punctate nuclear bodies. Isolation of the human cDNA and genomic DNA revealed that the gene was located on chromosome 8p21, a region implicated in numerous leukemias and solid tumors. Enforced expression of Hls5 in HeLa cells inhibited cell growth, clonogenicity, and tumorigenicity. It is conceivable that HLS5 is one of the tumor suppressor genes thought to reside at the 8p21 locus.
Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination1

The two main constraints that currently limit a broader usage of T cell therapy against viruses are the delay required to obtain specific T cells and the safety of the selection procedure. In the present work we developed a generally applicable strategy that eliminates the need for APC for timing reasons, and the need for infectious viral strains for safety concerns. As a model, we used the selection of T lymphocytes specific for the immunodominant CMV phosphoprotein pp65. PBMC from healthy seropositive donors were first depleted of IL-2R α-chain CD25+ cells and were then stimulated for 24–96 h with previously defined peptide Ags or with autologous PBMC infected with a canarypox viral vector encoding the total pp65 protein (ALVAC-pp65). Subsequent immunomagnetic purification of newly CD25-expressing cells allowed efficient recovery of T lymphocytes specific for the initial stimuli, i.e., for the already known immunodominant epitope corresponding to the peptides used as a model or for newly defined epitopes corresponding to peptides encoded by the transfected pp65 protein. Importantly, we demonstrated that direct PBMC stimulation allowed recovery not only of CD8+ memory T lymphocytes, but also of the CD4+ memory T cells, which are known to be crucial to ensure persistence of adoptively transferred immune memory. Finally, our analysis of pp65-specific T cells led to the identification of several new helper and cytotoxic epitopes. This work thus demonstrates the feasibility of isolating memory T lymphocytes specific for a clinically relevant protein without the need to prepare APC, to use infectious viral strains, or to identify immunodominant epitopes.
Human Oral Cavity as a Model for the Study of Genome-Genome Interactions

The enormous diversity of culturable bacteria within the oral microbial community coupled with experimental accessibility renders the human oral cavity a valuable model to investigate genome-genome interactions. The complex interactions of oral bacteria result in the formation of biofilms on the surfaces of the oral cavity. One mechanism thought to be important in biofilm formation is the coaggregation of bacterial partners. In this paper, we examine the role of coaggregation in oral biofilms and develop protocols to elucidate the spatial organization of bacterial species retained within oral biofilms. To explore these issues, we have employed two experimental systems: the saliva-coated flowcell and the retrievable enamel chip. From flowcell studies, we have determined that coaggregation can greatly influence the ability of an oral bacterial species to grow and be retained within the developing biofilm. To examine the spatial architecture of oral biofilms, fluorescent in situ hybridization protocols were developed that successfully target specific members of the oral microbial community. Together, these approaches provide insight into the development of oral biofilms and expand our understanding of genome-genome interactions.
AtVPS45 Is a Positive Regulator of the SYP41/SYP61/VTI12 SNARE Complex Involved in Trafficking of Vacuolar Cargo1[OA]

We report a functional characterization of AtVPS45 (for vacuolar protein sorting 45), a protein from the Sec1/Munc18 family in Arabidopsis (Arabidopsis thaliana) that interacts at the trans-Golgi network (TGN) with the SYP41/SYP61/VTI12 SNARE complex. A null allele of AtVPS45 was male gametophytic lethal, whereas stable RNA interference lines with reduced AtVPS45 protein levels had stunted growth but were viable and fertile. In the silenced lines, we observed defects in vacuole formation that correlated with a reduction in cell expansion and with autophagy-related defects in nutrient turnover. Moreover, transport of vacuolar cargo with carboxy-terminal vacuolar sorting determinants was blocked in the silenced lines, suggesting that AtVPS45 functions in vesicle trafficking to the vacuole. These trafficking defects are similar to those observed in vti12 mutants, supporting a functional relationship between AtVPS45 and VTI12. Consistent with this, we found a decrease in SYP41 protein levels coupled to the silencing of AtVPS45, pointing to instability and malfunction of the SYP41/SYP61/VTI12 SNARE complex in the absence of its cognate Sec1/Munc18 regulator. Based on its localization on the TGN, we hypothesized that AtVPS45 could be involved in membrane fusion of retrograde vesicles recycling vacuolar trafficking machinery. Indeed, in the AtVPS45-silenced plants, we found a striking alteration in the subcellular fractionation pattern of vacuolar sorting receptors, which are required for sorting of carboxy-terminal vacuolar sorting determinant-containing cargo. We propose that AtVPS45 is essential for recycling of the vacuolar sorting receptors back to the TGN and that blocking this step underlies the defects in vacuolar cargo trafficking observed in the silenced lines.
Ensemble simulations: folding, unfolding and misfolding of a high-efficiency frameshifting RNA pseudoknot

Abstract Massive all-atom molecular dynamics simulations were conducted across a distributed computing network to study the folding, unfolding, misfolding and conformational plasticity of the high-efficiency frameshifting double mutant of the 26 nt potato leaf roll virus RNA pseudoknot. Our robust sampling, which included over 40 starting structures spanning the spectrum from the extended unfolded state to the native fold, yielded nearly 120 μs of cumulative sampling time. Conformational microstate transitions on the 1.0 ns to 10.0 μs timescales were observed, with post-equilibration sampling providing detailed representations of the conformational free energy landscape and the complex folding mechanism inherent to the pseudoknot motif. Herein, we identify and characterize two alternative native structures, three intermediate states, and numerous misfolded states, the latter of which have not previously been characterized via atomistic simulation techniques. While in line with previous thermodynamics-based models of a general RNA folding mechanism, our observations indicate that stem-strand-sequence-separation may serve as an alternative predictor of the order of stem formation during pseudoknot folding. Our results contradict a model of frameshifting based on structural rigidity and resistance to mechanical unfolding, and instead strongly support more recent studies in which conformational plasticity is identified as a determining factor in frameshifting efficiency.
Effect of Hypotension and Carbon Dioxide Changes in an Improved Genuine Closed Cranial Window Rat Model

The genuine closed cranial window model, in which the thinned parietal bone constitutes the covering of the preparation, has contributed to a better understanding of the pathophysiological mechanisms in migraine. In its present form, only measurements of the middle meningeal artery (MMA) are performed. The aim of this study was, in addition, to measure pial artery/arteriole (PA) diameter and cortical cerebral blood flux in the same cranial window. The model was evaluated by studying the effects of hypotension and changes in arterial carbon dioxide pressure (PaCO2), because these parameters might influence the interpretation of pharmacological experiments. Out of 23 successful experiments it was possible to measure all three parameters in 19 animals. In four, PA diameter could not be measured, while MMA diameter and local cortical cerebral blood flux (LCBFFlux) always could. Haemorrhage-induced hypotension (-64 + 0.8 mmHg) caused an increase of MMA diameter of 11.8 + 8.4%, PA diameter of 61.2 + 7.7% and a decrease in LCBFFlux of - 36.4 + 2.5%. The decrease in blood pressure did not significantly change the MMA (P = 0.38); however, the PA diameter and the LCBF-Flux were affected (P < 0.001). All three parameters were sensitive to hypo- and hypercapnia. In conclusion, we have shown that not only MMA but also PA diameter and LCBFFlux can be measured in the same cranial window. Tight control of PaCO2 is essential in pharmacological experiments. If test substances possess hypotensive actions, it may be difficult to interpret whether the PA dilation is caused by the induced hypotension per se or is a direct pharmacological action or a combination. In contrast, the MMA does not autoregulate and MMA diameter changes in pharmacological studies may exclusively be due to direct pharmacological effects.
Sorbitan Sesquioleate, a Common Emulsifier in Topical Corticosteroids, Is an Important Contact Allergen

Background: In the past, sorbitan sesquioleate (SSO) was reported as an uncommon allergen, but recent data suggest SSO may be an important sensitizer. Objective: To present data on 13 of 112 dermatitis patients who reacted to SSO and/or sorbitan monooleate (SMO) on patch testing. Methods: A retrospective data analysis was conducted on data from 112 dermatitis patients patch‐tested from December 2006 to May 2007. All patients were tested with a modified North American Contact Dermatitis Group standard series, a cosmetic series, and a fragrance series. Results: Of 112 patients, 10 (8.9%) reacted to SSO, 1 (0.9%) to SMO, and 2 (1.8%) to both. Nine of 12 (75%) SSO‐positive patients were using topical corticosteroids emulsified with sorbitan derivatives or sorbitol; 2 of the 13 sorbitan‐allergic patients were allergic to one or more corticosteroid screening chemicals tested. Conclusion: SSO is a common emulsifier derived from sorbitol and is used in many high‐ to super‐potent corticosteroids. It has only recently been identified as an important contact allergen. The high prevalence of reactions to sorbitol derivatives in this small group of patients suggests that these chemicals may be sensitizing when applied to dermatitic skin. Larger studies should be conducted to confirm these findings.
Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop

Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system. Inhibition of CCR5, the cognate receptor of CCL5, or neutralization of CCL5, broke the metabolic loop and decreased cancer cell migration and EMT. Inhibition of aerobic glycolysis significantly reduced breast cancer cell EMT, indicated that aerobic glycolysis was necessary for the invasive phenotype of cancer cells. We further showed that TGF-β signaling regulated the expression of CCR5 in the co-culture system, and CCL5 induced glycolysis by mediation of AMPK signaling. The expression of CCL5-CCR5 axis was highly associated with macrophage infiltration, TGF-β and p-AMPK in clinical samples. CCL5-CCR5 axis promoted breast cancer metastasis in vivo. Our findings suggested a pivotal role of CCL5-CCR5 axis in the metabolic communication between cancer cells and macrophages.
Enhanced pressor response to angiotensin I in normotensive men with the deletion genotype (DD) for angiotensin-converting enzyme.

The insertion (I)/deletion (D) polymorphism of the human angiotensin-converting enzyme gene has emerged as a genetic risk factor for ischemic heart disease. However, the functional consequences of this polymorphism in humans are not known. Ten normotensive men with the DD genotype and 10 with the II genotype participated in a study in which pressor responses to stepwise infusions of incremental doses of angiotensin I (Ang I) and Ang II and Ang II production during Ang I infusion were measured. Pressor responses were expressed as PD20, which reflects the angiotensin dose required to raise mean blood pressure by 20 mm Hg. The PD20 for Ang I in subjects with the DD genotype was significantly lower than that in II genotype subjects (8.8 versus 14.8 ng/kg per minute, P = .0091), whereas the PD20 for Ang II between the two groups did not differ significantly. The ratio of PD20 for Ang I and Ang II in DD subjects was significantly lower than that in II subjects (0.85 versus 0.96, P = .0452), and the venous levels of Ang II during Ang I infusion in DD subjects were significantly higher than those in II subjects (P < .01). Our study has shown increased pressor responsiveness to Ang I, probably as a consequence of the generation of increased Ang II levels, in subjects homozygous for the DD allele of the angiotensin-converting enzyme gene. This result may be relevant to the reported adverse cardiovascular risk conferred by the D allele, as it provides a mechanistic rationale for the association between this polymorphism and cardiovascular disease.