Miracle-dz/UniFAR-FTUs huggingface dataset:
Synaptojanin1 Modifies Endolysosomal Parameters in Cultured Ventral Midbrain Neurons

Abstract The accumulation of α-synuclein (α-syn)-enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5’-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency (Synj1+/−) leads to accumulation of the autophagy substrate p62 and pathologic α-syn proteins in the midbrain (MB) and striatum of aged mice. In this study, we aim to investigate the neuronal degradation pathway using the Synj1+/− MB culture from mouse pups of mixed sex as a model. Our data show that GFP-LC3 puncta formation and cumulative mKeima puncta formation are unaltered at baseline in Synj1+/− MB neurons. However, GFP-LAMP1 puncta is reduced with a similar decrease in endogenous proteins, including lysosomal-associated membrane protein (LAMP)1, LAMP2, and LAMP2A. The LAMP1 vesicles are hyperacidified with enhanced enzymatic activity in Synj1+/− MB neurons. Using a combination of light and electron microscopy (EM), we show that endolysosomal changes are primarily associated with a lack of SAC1 activity. Consistently, expressing the SYNJ1 R258Q mutant in N2a cells reduces the lysosome number. Interestingly, the endolysosomal defects in Synj1+/− neurons does not impact the clearance of exogenously expressed wild-type (WT) α-syn; however, the clearance of α-syn A53T was impaired in the axons of Synj1+/− MB neurons. Taken together, our results suggest axonal vulnerability to endolysosomal defects in Synj1-deficient MB neurons.
Functional Ability, Psychological Factors, and Rehabilitation Outcomes After Elective Total Hip Replacement

Background. The role of positive psychological factors in acute rehabilitation after total hip replacement (THR) is unclear. Purpose. (a) Examine the trajectory of functional ability among older adults after THR from presurgery to discharge from acute rehabilitation and (b) determine which physical and psychological factors at admission would predict functional ability at discharge and length of stay in rehabilitation. Methods. This prospective cohort study included 30 participants (age M = 76.20 years) from an inpatient geriatric rehabilitation center. They completed the Geriatric Depression Scale and Positive Affect questionnaire. The FIM® Motor domain of Functional Independent Measure (mFIM) was recorded presurgery, at admission, and upon discharge. Findings. Functional ability improved at discharge; however, the presurgery functional ability was not regained. Positive affect explained the length of stay in rehabilitation above and beyond the presurgery mFIM. Implications. Occupational therapists should improve ways to enhance self-care and positive affect in acute rehabilitation.
The Association of Cognitive Impairment With Depressive Symptoms, Function, and Pain in Hospitalized Older Patients With Dementia

This study examined the associations between cognition and depressive symptoms, function, and pain among hospitalized older patients with dementia. We utilized baseline data of 461 hospitalized older patients with dementia who participated in an intervention study implementing Family-centered Function-focused Care (Fam-FFC) and conducted stepwise linear regression. On average, the participants (males = 189; 41% and females = 272; 59%) were 81.64 years old (Standard Deviation, SD = 8.38). There was a statistically significant association of cognition with depressive symptoms (b = −0.184, p < .001), functional status (b = 1.324, p < .001), and pain (b = −0.045, p < .001) when controlling for covariates. This study utilized a large sample of a relatively underrepresented population, hospitalized older adults with dementia, and addressed a topic with great clinical significance. Specific focus on testing and implementing best practices or interventions to support the clinical outcomes, and the cognitive function of hospitalized older adults with dementia is warranted in both practice and research.
Impact of the Next-Nearest-Neighbor Interaction on Traffic Flow of Highway with Slopes

In this paper, we study the motion course of traffic flow on the slopes of a highway by applying a microscopic traffic model, which takes into account the next-nearest-neighbor interaction in an intelligent transportation system environment. Three common gradients of the highway, which are sag terrain, uphill terrain, and downhill terrain on a single-lane roadway, are selected to clarify the impact on the traffic flow by the next-nearest-neighbor interaction in relative velocity. We obtain the current-density relation for traffic flow on the sag, the uphill and the downhill under the next-nearest-neighbor interaction strategy. It is observed that the current saturates when the density is greater than a critical value and the current decreases when the density is greater than another critical value. When the density falls into the intermediate range between the two critical densities it is also found that the oscillatory jam, easily leads to traffic accidents, often appears in the downhill stage, and the next-nearest-neighbor interaction in relative velocity has a strong suppressing effect on this kind of dangerous congestion. A theoretical analysis is also presented to explain this important conclusion.
An HMM approach expands the landscape of sesquiterpene cyclases across the kingdom Fungi

Sesquiterpene cyclases (STC) catalyse the cyclization of the C15 molecule farnesyl diphosphate into a vast variety of mono- or polycyclic hydrocarbons and, for a few enzymes, oxygenated structures, with diverse stereogenic centres. The huge diversity in sesquiterpene skeleton structures in nature is primarily the result of the type of cyclization driven by the STC. Despite the phenomenal impact of fungal sesquiterpenes on the ecology of fungi and their potentials for applications, the fungal sesquiterpenome is largely untapped. The identification of fungal STC is generally based on protein sequence similarity with characterized enzymes. This approach has improved our knowledge on STC in a few fungal species, but it has limited success for the discovery of distant sequences. Besides, the tools based on secondary metabolite biosynthesis gene clusters have shown poor performance for terpene cyclases. Here, we used four sets of sequences of fungal STC that catalyse four types of cyclization, and specific amino acid motives to identify phylogenetically related sequences in the genomes of basidiomycetes fungi from the order Polyporales. We validated that four STC genes newly identified from the genome sequence of Leiotrametes menziesii, each classified in a different phylogenetic clade, catalysed a predicted cyclization of farnesyl diphosphate. We built HMM models and searched STC genes in 656 fungal genomes genomes. We identified 5605 STC genes, which were classified in one of the four clades and had a predicted cyclization mechanism. We noticed that the HMM models were more accurate for the prediction of the type of cyclization catalysed by basidiomycete STC than for ascomycete STC.
Causal Effects of Stochastic PrEP Interventions on HIV Incidence Among Men Who Have Sex With Men

Abstract Antiretroviral preexposure prophylaxis (PrEP) is highly effective in preventing human immunodeficiency virus (HIV) infection, but uptake has been limited and inequitable. Although interventions to increase PrEP uptake are being evaluated in clinical trials among men who have sex with men (MSM), those trials cannot evaluate effects on HIV incidence. Estimates from observational studies of the causal effects of PrEP-uptake interventions on HIV incidence can inform decisions about intervention scale-up. We used longitudinal electronic health record data from HIV-negative MSM accessing care at Fenway Health, a community health center in Boston, Massachusetts, from January 2012 through February 2018, with 2 years of follow-up. We considered stochastic interventions that increased the chance of initiating PrEP in several high-priority subgroups. We estimated the effects of these interventions on population-level HIV incidence using a novel inverse-probability weighted estimator of the generalized g-formula, adjusting for baseline and time-varying confounders. Our results suggest that even modest increases in PrEP initiation in high-priority subgroups of MSM could meaningfully reduce HIV incidence in the overall population of MSM. Interventions tailored to Black and Latino MSM should be prioritized to maximize equity and impact.
Impact of Arm Dominance and Location on Detecting Electrotactile Stimuli During Voluntary Motor Activation in Older Adults

Activation-related sensory gating is important for sensorimotor control, filtering signals irrelevant to a task. Literature on brain lateralization suggests that motor activation patterns during sensorimotor control differ depending on arm dominance. Whether the lateralization effect extends to how sensory signals modulate during voluntary sensorimotor control remains unaddressed. We compared tactile sensory gating during voluntary motor activation between the arms of older adults. Eight right-arm dominant participants received a single-pulse, 100 $\mu$s square-wave electrotactile stimulus at their testing arm's fingertip or elbow. We identified at both arms the threshold at which the electrotactile stimulus was detected when participants were at rest (baseline) and isometrically flexing about the elbow to 25% and 50% of their maximum voluntary torque. Results reveal a difference in the detection threshold at the fingertip (p $< $ 0.001) between the arms, yet not the elbow (p = 0.264). Additionally, results demonstrate that greater isometric flexion about the elbow yields increased detection thresholds at the elbow (p = 0.005), yet not the fingertip (p = 0.069). However, the changes in detection threshold during motor activation did not significantly differ between the arms (p = 0.154). The findings regarding an impact of arm dominance and location on tactile perception are important when considering sensorimotorhaptic perception and training, including post-unilateral injury.
Norovirus Disease Among Children <5 Years in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015–2018

Abstract Background To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. Methods Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0–59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. Results From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6–8 months with majority (61.2%) aged 6–11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. Conclusions Infants aged 6–11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.
Comparison of Isoenzyme Pattern of Echinococcus granulosus sensu stricto (G1-G3) and E. canadensis (G6/G7) Protoscoleces

Background: Different genotypes of Echinococcus granulosus s.l. infect humans and ungulate animals, causing cystic echinococcosis. Simultaneous isoenzyme, as well as molecular characterizations of this parasite, has not yet been investigated in Iran. The present study aimed to evaluate the isoenzyme pattern of the E. granulosus s.s. and E. canadensis genotypes in Iran. Methods: A total of 32 (8 humans and 24 animals) cystic echinococcosis cysts were isolated from Shiraz, Tehran, Ilam, and Birjand from May 2018 to December 2020. The DNAs were extracted and their genotypes were determined by molecular methods. Enzymes were extracted from the cysts and subjected to polyacrylamide gel electrophoresis. The activities of G6PD, MDH, ME, NH1, and ICD were examined in the cyst samples using isoenzyme method and compared it with the genotyping findings. Results: DNA sequence analysis of the samples showed that the specimens contained 75% E. granulosus s.s. (G1) and 25% E. canadensis (G6) genotypes. The isoenzyme pattern of ICD in both genotypes produced a six-band pattern with different relative factors. The G6PD also produced two bands with different relative migrations in both genotypes. The MDH and NH1 systems revealed a two-band pattern, while only one band was generated in the ME enzyme in the E. granulosus s.s. genotype. In the E. canadensis, the MDH and NH1 enzymes showed one band, and the ME enzyme represented a two-band pattern. Conclusion: Our findings suggest that E. granulosus s.s. and E. canadensis genotypes have entirely different isoenzyme patterns for NH1, G6PD, MDH, and ME.
Embryonic factors mediate the maternal age-induced programming of offspring postnatal behavior in mice

Abstract Advanced maternal age is associated with adverse pregnancy and offspring outcomes, including neurodevelopmental disorders. While age-related oocyte and embryonic abnormalities may underlie this association, the aged maternal uterine environment also plays an important role in offspring development and survival. The aim of this study was to evaluate the contribution of maternal age-related embryonic and uterine factors on pregnancy and offspring behavior, by using a model of reciprocal embryo transfer between old and young female mice. Pregnancies were obtained by transferring embryos collected from either old (9–14 months) or young (3–4 months) C57BL/6J female mice to either young or old recipients. The results showed that embryos from old and young donors have comparable developmental potential when transferred to young recipients, whereas no pregnancies were obtained by transferring embryos of young females to old recipients. Moreover, the offspring conceived by aged females displayed altered ultrasonic vocalization and learning skills compared to the progeny of young females, even though they were both prenatally and postnatally fostered by young recipients. These results indicate that maternal factors mostly determine the occurrence of age-related pregnancy complications, whereas the long-term effects of maternal aging on the offspring's behavior could be already established at pre-implantation stages and depend on embryonic factors. Summary Sentence Embryos conceived by old females develop normally when surgically transferred to young recipients. Offspring conceived by old females display altered behaviors, even though they were prenatally and postnatally fostered by young females.
Impaired muscle function, including its decline, is related to greater long‐term late‐life dementia risk in older women

Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late‐life dementia (after 80 years of age). We examined whether hand grip strength and timed‐up‐and‐go (TUG) performance, including their change over 5 years, were associated with late‐life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ4 (APOE ℇ4) genotype.
Hormone-regulated expansins: Expression, localization, and cell wall biomechanics in Arabidopsis root growth

Abstract Expansins facilitate cell expansion by mediating pH-dependent cell wall (CW) loosening. However, the role of expansins in controlling CW biomechanical properties in specific tissues and organs remains elusive. We monitored hormonal responsiveness and spatial specificity of expression and localization of expansins predicted to be the direct targets of cytokinin signaling in Arabidopsis (Arabidopsis thaliana). We found EXPANSIN1 (EXPA1) homogenously distributed throughout the CW of columella/lateral root cap, while EXPA10 and EXPA14 localized predominantly at 3-cell boundaries in the epidermis/cortex in various root zones. EXPA15 revealed cell-type-specific combination of homogenous vs. 3-cell boundaries localization. By comparing Brillouin frequency shift and AFM-measured Young's modulus, we demonstrated Brillouin light scattering (BLS) as a tool suitable for non-invasive in vivo quantitative assessment of CW viscoelasticity. Using both BLS and AFM, we showed that EXPA1 overexpression upregulated CW stiffness in the root transition zone (TZ). The dexamethasone-controlled EXPA1 overexpression induced fast changes in the transcription of numerous CW-associated genes, including several EXPAs and XYLOGLUCAN:XYLOGLUCOSYL TRANSFERASEs (XTHs), and associated with rapid pectin methylesterification determined by in situ Fourier-transform infrared spectroscopy in the root TZ. The EXPA1-induced CW remodeling is associated with the shortening of the root apical meristem, leading to root growth arrest. Based on our results, we propose that expansins control root growth by a delicate orchestration of CW biomechanical properties, possibly regulating both CW loosening and CW remodeling.
Gravitational Forces in Vectorial Relativity

It is known that Kepler’s Laws can be derived from the Newton’s Law of Universal Gravitation. For doing this, mass is considered as an invariable parameter. Although this consideration works wonderfully to solve most of problems in astronomy calculations, as well as in all physics, when astral body’s speeds are so high and very precise measurements are required, the referred Kepler Laws do not cope enough what is expected. That’s why the General Theory of Relativity materialized. As it was indirectly pointed out by Einstein in 1905, Newton and Kepler Laws do not consider the relativistic variation of mass with its velocity. The purpose of this review is to discuss the mathematical and theoretical physics underlying the development of the classical model as well as the presentation of an approach that naturally concludes with a modification of the Newton’s Universal Force of Gravitation in order to adapt its conception to a mass-variation modern view (relativistic). This work considers a generic variable mass, without establishing any cause of its variation (Einstenian, or any other). It is worth mentioning that although this approach was not worked under the Einstein’s General Theory of Relativity, but under a three-dimensional environment, it can be applied inside any relativistic gravitation theory, we discuss the conservation laws and the equations of motion in detail, and provide a number of (in our opinion) interesting and relevant applications.
Proteins Rpr2 and Pop3 increase the activity and thermal stability of yeast RNase P

ABSTRACT RNA-based enzyme RNase P is a ribonucleoprotein complex responsible primarily for 5’-maturation of tRNAs. S. cerevisiae RNase P comprises a catalytic RNA component and nine proteins. The assembly and maturation of S. cerevisiae RNase P involves an abundant and catalytically active precursor form, which includes all components except for proteins Rpr2 and Pop3. Rpr2 and Pop3 are essential proteins, but their roles in RNase P were not clear. Here we use a step-wise in vitro assembly of yeast RNase P to show that the addition of proteins Rpr2 and Pop3 increases the activity and thermal stability of the RNase P complex, similar to the effects previously observed for archaeal RNases P.
Can’t We Do Better? A cost-benefit analysis of proposal writing in a competitive funding environment

This article presents an analysis of third-party funding in Austria for energy research, including an analysis of the costs and benefits of writing proposals and of the trust proposal applicants place in the application process. For this purpose, applicants from research and industry applying for government-funded energy research grants in Austria were surveyed. Preparing a new proposal takes about 50 working days; at the current success rate, about 300 person-days are spent preparing proposals for a single proposal to be funded.More than 90% of researchers perceive that they currently spend too much time preparing proposals and only 10% of researchers believe that the current competitive third-party funding system has a positive effect on the quality of research. Furthermore, researchers have limited trust in the objectivity of proposal review processes.
STUDIES ON FACTORS AFFECTING CALVING INTERVAL IN TWO AND THREE BREED GIR CROSSES

A data on 2040 records of halfbreds (FG and JG) and three breed (FJG, JFG and BFG) Gir crosses were collected and analysed by least-squares method. The genetic group, period and season of calving, parity, age and weight at first calving were considered as sources of variation. The overall least-squares means for calving interval of first five lactations and their pooled were 419.60±4.38, 401.89±7.02, 401.32±5.82, 400.62±8.16, 387.33±12.58 and 403.45±3.45 days, respectively. The calving interval of first five lactations were non-significantly affected by all the sources of variation except genetic group effect (P<0.05) on first calving interval. The genetic group, lactation order (P<0.05) and period of calving (P<0.01) had significant effect on the pooled calving interval.