Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteoclast precursors in murine bone marrow express CD27 and are impeded in osteoclast development by CD70 on activated immune cells

Osteoclasts (OCs) are bone-resorbing cells that are formed from hematopoietic precursors. OCs ordinarily maintain bone homeostasis, but they can also cause major pathology in autoimmune and inflammatory diseases. Under homeostatic conditions, receptor activator of nuclear factor kappa-B (RANK) ligand on osteoblasts drives OC differentiation by interaction with its receptor RANK on OC precursors. During chronic immune activation, RANK ligand on activated immune cells likewise drives pathogenic OC differentiation. We here report that the related TNF family member CD70 and its receptor CD27 can also mediate cross-talk between immune cells and OC precursors. We identified CD27 on a rare population (0.3%) of B220−c-Kit+CD115+CD11blow cells in the mouse bone marrow (BM) that are highly enriched for osteoclastogenic potential. We dissected this population into CD27high common precursors of OC, dendritic cells (DCs) and macrophages and CD27low/neg downstream precursors that could differentiate into OC and macrophages, but not DC. In a recombinant mouse model of chronic immune activation, sustained CD27/CD70 interactions caused an accumulation of OC precursors and a reduction in OC activity. These events were due to a CD27/CD70-dependent inhibition of OC differentiation from the OC precursors by BM-infiltrating, CD70+-activated immune cells. DC numbers in BM and spleen were increased, suggesting a skewing of the OC precursors toward DC differentiation. The impediment in OC differentiation culminated in a high trabecular bone mass pathology. Mice additionally presented anemia, leukopenia, and splenomegaly. Thus, under conditions of constitutive CD70 expression reflecting chronic immune activation, the CD27/CD70 system inhibits OC differentiation and favors DC differentiation.
Simultaneous Enhancement of Electrical Conductivity and Thermopower of Bi2Te3 by Multifunctionality of Native Defects

Simultaneous increases in electrical conductivity (up to 200%) and thermopower (up to 70%) are demonstrated by introducing native defects in Bi2 Te3 films, leading to a high power factor of 3.4 × 10(-3) W m(-1) K(-2). The maximum enhancement of the power factor occurs when the native defects act beneficially both as electron donors and energy filters to mobile electrons. They also act as effective phonon scatterers.
High frequencies of diabetic micro- and macroangiopathies in patients with type 2 diabetes mellitus with decreased estimated glomerular filtration rate and normoalbuminuria.

BACKGROUND The clinical characteristics of diabetic patients presenting with normoalbuminuria with decreased kidney functions were investigated. METHODS A cross-sectional study was performed in 1197 patients with type 2 diabetes mellitus. The estimated glomerular filtration rate (eGFR) was calculated using the formula recommended by the Japanese Society of Nephrology. RESULTS The groups with normoalbuminuria, microalbuminuria, macroalbuminuria and renal failure consisted of 696 (58%), 229 (19%), 196 (16%) and 76 (6%) subjects, respectively. The frequencies of all diabetic micro- and macroangiopathies increased with progression of diabetic nephropathy stage. However, in the groups with chronic kidney disease (CKD) stage 3+4 (60 > eGFR > or = 15 mL/min/1.73 m(2)), the frequencies of diabetic neuropathy and macroangiopathies were not different among the groups staged by urinary albumin excretion. In the normoalbuminuria group, 223 (32%) cases showed CKD stage 3+4. Diabetic neuropathy and macroangiopathies were significantly more frequent in the groups presenting with normoalbuminuria with CKD stage 3+4 than in those with CKD stage 1+2 (eGFR > or = 60 mL/min/1.73 m(2)). The patients' age, duration of diabetes mellitus and frequency of hypertension were significantly higher in the groups presenting with normoalbuminuria with CKD stage 3+4. After adjustment by age, grade of albuminuria or both, CKD stage 3+4 was an independent risk factor for some diabetic complications. CONCLUSIONS The combination of urinary albumin excretion and eGFR is useful for earlier detection of kidney and vascular damage in patients with diabetes mellitus. Evaluation of eGFR should be performed for all diabetic patients even if they show normoalbuminuria.
Sprouty genes function in suppression of prostate tumorigenesis

Expression of Sprouty genes is frequently decreased or absent in human prostate cancer, implicating them as suppressors of tumorigenesis. Here we show they function in prostate tumor suppression in the mouse. Concomitant inactivation of Spry1 and Spry2 in prostate epithelium causes ductal hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN). However, when Spry1 and Spry2 loss-of-function occurs in the context of heterozygosity for a null allele of the tumor suppressor gene Pten, there is a striking increase in PIN and evidence of neoplastic invasion. Conversely, expression of a Spry2 gain-of-function transgene in Pten null prostatic epithelium suppresses the tumorigenic effects of loss of Pten function. We show that Sprouty gene loss-of-function results in hyperactive RAS/ERK1/2 signaling throughout the prostate epithelium and cooperates with heterozygosity for a Pten null allele to promote hyperactive PI3K/AKT signaling. Furthermore, Spry2 gain-of-function can suppress hyperactivation of AKT caused by the absence of PTEN. Together, these results point to a key genetic interaction between Sprouty genes and Pten in prostate tumorigenesis and provide strong evidence that Sprouty genes can function to modulate signaling via the RAS/ERK1/2 and PI3K/AKT pathways. The finding that Sprouty genes suppress tumorigenesis caused by Pten loss-of-function suggests that therapeutic approaches aimed at restoring normal feedback mechanisms triggered by receptor tyrosine kinase signaling, including Sprouty gene expression, may provide an effective strategy to delay or prevent high-grade PIN and invasive prostate cancer.
Effects of mycophenolate mofetil on acute ischaemia-reperfusion injury in rats and its consequences in the long term.

BACKGROUND Renal ischaemia-reperfusion injury (IRI) acutely decreases glomerular filtration rate (GFR) and impairs kidney function in the long term. Pre-treatment with chaetomellic acid (KM), an inhibitor of membrane-bound Ha-Ras, has demonstrated beneficial effects on acute renal ischaemia. METHODS We tested whether mycophenolate mofetil (MMF, 20 mg/day for 4 days before IRI), an immunosuppressor with anti-inflammatory properties, improved renal outcome in uninephrectomized rats after IRI (45 min of renal ischaemia), alone or in combination with KM. RESULTS One day after ischaemia, GFR was markedly depressed in untreated rats (-75% vs. normal rats, P < 0.001), and pre-treatment with MMF did not modify this fall (-75%, P < 0.001 vs. normal). KM (0.23 microg/kg before IRI) greatly prevented GFR loss (-39% vs. normal, P < 0.05), but its action was not further improved by the combined administration with MMF (GFR, -45% vs. normal, P < 0.05). MMF significantly reduced ICAM-1 expression and monocyte recruitment (P < 0.05 vs. untreated rats); nevertheless, renal histology of MMF rats was similar to that of untreated rats. Additional rats were examined 6 months after IRI: untreated rats with IRI showed reduced renal function (-42% vs. normal, P < 0.01) and proteinuria (P < 0.001 vs. normal); rats pre-treated with MMF showed a similar pattern, whereas rats treated with KM before IRI presented a better GFR (-20% vs. normal, not significant) and near-normal values of proteinuria. The combination of KM + MMF gained the same results. CONCLUSIONS Pre-treatment with MMF before IRI does not confer functional or morphological protection to the kidney, despite the reduced expression of some inflammatory markers. The combination of MMF + KM does not offer additional advantages to solitary KM treatment.
TRPM8 activation attenuates inflammatory responses in mouse models of colitis

Transient Receptor Potential Melastatin–8 (TRPM8), a recently identified member of the transient receptor potential (TRP) family of ion channels, is activated by mild cooling and by chemical compounds such as the supercooling agent, icilin. Since cooling, possibly involving TRPM8 stimulation, diminishes injury-induced peripheral inflammation, we hypothesized that TRPM8 activation may also attenuate systemic inflammation. We thus studied the involvement of TRPM8 in regulating colonic inflammation using two mouse models of chemically induced colitis. TRPM8 expression, localized immunohistochemically in transgenic TRPM8GFP mouse colon, was up-regulated in both human- and murine-inflamed colon samples, as measured by real-time PCR. Wild-type mice (but not TRPM8-nulls) treated systemically with the TRPM8 agonist, icilin showed an attenuation of chemically induced colitis, as reflected by a decrease in macroscopic and microscopic damage scores, bowel thickness, and myeloperoxidase activity compared with untreated animals. Furthermore, icilin treatment reduced the 2,4,6-trinitrobenzenesulfonic acid–induced increase in levels of inflammatory cytokines and chemokines in the colon. In comparison with wild-type mice, Dextran Sodium Sulfate (DSS)-treated TRPM8 knockout mice showed elevated colonic levels of the inflammatory neuropeptide calcitonin-gene–related peptide, although inflammatory indices were equivalent for both groups. Further, TRPM8 activation by icilin blocked capsaicin-triggered calcitonin-gene–related peptide release from colon tissue ex vivo and blocked capsaicin-triggered calcium signaling in Transient Receptor Potential Vaniloid-1 (TRPV1) and TRPM8 transfected HEK cells. Our data document an anti-inflammatory role for TRPM8 activation, in part due to an inhibiton of neuropeptide release, pointing to a novel therapeutic target for colitis and other inflammatory diseases.
Organisational culture and routine midwifery practice on labour ward: implications for mother-baby contact

This study examines labour ward culture on two British labour wards, in terms of mother-baby contact and breastfeeding, which has not been empirically researched in the UK since 1985 (Garforth & Garcia 1989). Aims: to investigate the organisational culture; examine mothers’ beliefs and experiences; and midwives’ knowledge, beliefs and practices. Objectives: To compare organisational cultures; identify if midwifery practice is evidence based and factors which facilitate or detract from it; identify mothers’ preferences, beliefs and levels of satisfaction. Study Design: Ethnography with case study and diagnostic analysis also utilised. Methods: observation and interviews: purposive sample of mothers (n = 50) and midwives (n = 51); Results: Mother-baby contact after birth is usually interrupted for completion of tasks and some babies have multiple contact episodes, which has not been previously described in the literature. Completion of routine tasks for transfer of mothers and babies to postnatal ward takes precedence, because of organisational demands and insufficient resources. However, most mothers expressed feeling satisfied with contact achieved. Conclusion: Findings of the study have contributed new insights and knowledge of labour ward culture. It is not conducive to uninterrupted mother-baby contact and is not evidence-based. Recommendations: The development of a learning culture and clinical leadership to promote evidence-based practice and woman-centred care is recommended. The unique period after birth should not be disturbed, to prioritise routine tasks.
Generalized reproduction numbers and the prediction of patterns in waterborne disease

Understanding, predicting, and controlling outbreaks of waterborne diseases are crucial goals of public health policies, but pose challenging problems because infection patterns are influenced by spatial structure and temporal asynchrony. Although explicit spatial modeling is made possible by widespread data mapping of hydrology, transportation infrastructure, population distribution, and sanitation, the precise condition under which a waterborne disease epidemic can start in a spatially explicit setting is still lacking. Here we show that the requirement that all the local reproduction numbers be larger than unity is neither necessary nor sufficient for outbreaks to occur when local settlements are connected by networks of primary and secondary infection mechanisms. To determine onset conditions, we derive general analytical expressions for a reproduction matrix , explicitly accounting for spatial distributions of human settlements and pathogen transmission via hydrological and human mobility networks. At disease onset, a generalized reproduction number (the dominant eigenvalue of ) must be larger than unity. We also show that geographical outbreak patterns in complex environments are linked to the dominant eigenvector and to spectral properties of . Tests against data and computations for the 2010 Haiti and 2000 KwaZulu-Natal cholera outbreaks, as well as against computations for metapopulation networks, demonstrate that eigenvectors of provide a synthetic and effective tool for predicting the disease course in space and time. Networked connectivity models, describing the interplay between hydrology, epidemiology, and social behavior sustaining human mobility, thus prove to be key tools for emergency management of waterborne infections.
Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness

Rapid eye movement (REM) sleep constitutes a distinct “third state” of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.
CH3NH3PbBr3–CH3NH3PbI3 Perovskite–Perovskite Tandem Solar Cells with Exceeding 2.2 V Open Circuit Voltage

Perovskite-perovskite tandem solar cells with open-circuit voltages of over 2.2 V are reported. These cost-effective, solution-processible perovskite hybrid tandem solar cells with high open-circuit voltages are fabricated by the simple lamination of a front planar MAPbBr3 perovskite cell and a back MAPbI3 planar perovskite solar cell.
A descriptive study to examine the needs of kinship care providers

of A DESCRIPTIVE STUDY TO EXAMINE THE NEEDS OF KINSHIP CARE PROVIDERS by Xavier Maldonado Wendy Rebentisch This study examined the importance of support systems for kinship providers and identified gaps in the system of care for children in kinship care. The study used a nonrandom purposive sample of 45 professionals working with kinship care providers in Sacramento County. The study findings indicate the importance of increased financial support, training for kinship providers to understand the dynamics of caring for kin, increased access to services and social service professionals’ increased involvement through consistent home visits and supervision. The authors recommend interventions and preventive measures at each of the areas listed above. Both the researchers worked jointly to formulate the study problem, specify the research question, and shared the responsibilities of conducting literature review, developing the questionnaire for data collection, data analysis and writing the project report. ___________________________________, Committee Chair Jude Antonyappan, Ph.D., MSW ___________________________ Date
Characterization of the free-energy landscapes of proteins by NMR-guided metadynamics

The use of free-energy landscapes rationalizes a wide range of aspects of protein behavior by providing a clear illustration of the different states accessible to these molecules, as well as of their populations and pathways of interconversion. The determination of the free-energy landscapes of proteins by computational methods is, however, very challenging as it requires an extensive sampling of their conformational spaces. We describe here a technique to achieve this goal with relatively limited computational resources by incorporating nuclear magnetic resonance (NMR) chemical shifts as collective variables in metadynamics simulations. As in this approach the chemical shifts are not used as structural restraints, the resulting free-energy landscapes correspond to the force fields used in the simulations. We illustrate this approach in the case of the third Ig-binding domain of protein G from streptococcal bacteria (GB3). Our calculations reveal the existence of a folding intermediate of GB3 with nonnative structural elements. Furthermore, the availability of the free-energy landscape enables the folding mechanism of GB3 to be elucidated by analyzing the conformational ensembles corresponding to the native, intermediate, and unfolded states, as well as the transition states between them. Taken together, these results show that, by incorporating experimental data as collective variables in metadynamics simulations, it is possible to enhance the sampling efficiency by two or more orders of magnitude with respect to standard molecular dynamics simulations, and thus to estimate free-energy differences among the different states of a protein with a kBT accuracy by generating trajectories of just a few microseconds.
Moncrief-Popovich technique is an advantageous method of peritoneal dialysis catheter implantation.

BACKGROUND A safe and well-functioning peritoneal catheter is fundamental for adequate peritoneal dialysis (PD) treatment. Peritoneal catheter implantation by Moncrief-Popovich (MP) technique might add several clinical advantages besides allowing timely access implantation. The aim of this study was to investigate the rate of catheter-related complications and survival in a single-centre university hospital PD unit, according to the method of catheter implantation. METHODS Four hundred and sixty-seven consecutive Tenckhoff catheters were implanted after antibiotic prophylaxis in an operating room: surgical mini-laparotomy (ML) was used in 211 (45%), Seldinger technique (S) in 76 (16%) and mini-laparotomy with MP method in 180 (38.5%). RESULTS The MP technique was significantly associated with a lower rate of early exit-site infection (ESI) (P = 0.02), lower rate of leak (P < 0.0001) and also lower rate of obstruction (P = 0.034) in spite of prolonged break-in (median 55 days, range 0-991 days). Catheter survival by MP technique was 92%, 83% and 64% at 12, 24 and 60 months, respectively, and significantly superior in comparison with the previous methods (log-rank, P = 0.032). By Cox multivariate analysis, adjusted for age, sex and diabetes, the MP technique remained independently associated with better catheter survival [hazard ratio (HR) 0.587 (0.397-0.870), P = 0.008]. CONCLUSION Our experience documented improved PD clinical outcomes with the MP method of catheter implantation while assuring timely access management and logistic advantages.
Kohl and surma eye cosmetics as significant sources of lead (Pb) exposure

Abstract Kohl (surma) is a traditional eye cosmetic used in the Middle East, India, Pakistan, and parts of Africa that often contains high levels of lead (Pb), a developmental neurotoxicant. Many researchers have called for stricter governmental regulations of kohl trade and quality control and improved public education regarding its hazards and some governments have adopted import controls and educational campaigns to alert users to the hazards of using Pb-­-containing kohl. However, users remain unaware of the hazards of kohl usage, and some authorities minimize its potential danger. In this review, we summarize available data from the peer-­-reviewed literature on prevalence and attitudes regarding kohl use, Pb content of kohl samples from many sources, potential routes of entry of Pb into the body from kohl, and epidemiologic evidence that kohl is a source of Pb exposure in infants and women. Chemical analyses show that kohl has a wide range of formulae, with some containing PbS as the principal ingredient and others based on carbon and often Pb-­-free. Ocular, dermal, or gastrointestinal routes of entry of Pb into the body from kohl had been insufficiently studied to rule any of them out. The preponderance of epidemiologic evidence supports the conclusion that Pb-­-based kohl is associated with increased PbB in women who use kohl and their children.
Misplaced helix slows down ultrafast pressure-jump protein folding

Using a newly developed microsecond pressure-jump apparatus, we monitor the refolding kinetics of the helix-stabilized five-helix bundle protein λ*YA, the Y22W/Q33Y/G46,48A mutant of λ-repressor fragment 6–85, from 3 μs to 5 ms after a 1,200-bar P-drop. In addition to a microsecond phase, we observe a slower 1.4-ms phase during refolding to the native state. Unlike temperature denaturation, pressure denaturation produces a highly reversible helix-coil-rich state. This difference highlights the importance of the denatured initial condition in folding experiments and leads us to assign a compact nonnative helical trap as the reason for slower P-jump–induced refolding. To complement the experiments, we performed over 50 μs of all-atom molecular dynamics P-drop refolding simulations with four different force fields. Two of the force fields yield compact nonnative states with misplaced α-helix content within a few microseconds of the P-drop. Our overall conclusion from experiment and simulation is that the pressure-denatured state of λ*YA contains mainly residual helix and little β-sheet; following a fast P-drop, at least some λ*YA forms misplaced helical structure within microseconds. We hypothesize that nonnative helix at helix-turn interfaces traps the protein in compact nonnative conformations. These traps delay the folding of at least some of the population for 1.4 ms en route to the native state. Based on molecular dynamics, we predict specific mutations at the helix-turn interfaces that should speed up refolding from the pressure-denatured state, if this hypothesis is correct.