Miracle-dz/UniFAR-FTUs huggingface dataset:
Response inhibition predicts poor antidepressant treatment response in very old depressed patients.

OBJECTIVE There have been mixed findings regarding the prognostic significance of age of onset, executive dysfunction, and hyperintensity burden on treatment outcome in late-life depression. METHODS Growth curve models were fit to data from the only 8-week, double-blind, placebo controlled trial of citalopram (20-40 mg/day) in patients aged 75 years and older with unipolar depression. Baseline assessment included Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (to determine age at onset), Stroop Color-Word Test (to assess the response inhibition component of execution dysfunction), and structural magnetic resonance imaging (to determine hyperintensity burden). RESULTS In the citalopram condition, patients with response inhibition (most impaired quartile) scored higher at endpoint than those without response inhibition. There were no effects for age of onset or hyperintensity load on response in the citalopram condition. In the placebo condition, patients with early-onset depression had higher depression scores at endpoint than patients with late-onset depression. CONCLUSION Only response inhibition, a fundamental executive function, predicted poor treatment response to antidepressant medication. Although patients with response inhibition also showed deficits in reaction time, adjusting for reaction time in our final response inhibition model did not substantively change the findings.
Colonial Containment? Repression of Pro-Independence Street Demonstrations in Algiers, Casablanca and Paris, 1945–1962

This article draws on three examples of the violent repression of pro-independence nationalist street demonstrations: Casablanca, 7–8 December 1952; Algiers, 10–13 December 1960; Paris, 17 October 1961. Changes in the urban landscape due to migration, urban planning and housing policy brought the threat perceptions of the colonial authorities to centre upon certain poor districts and their inhabitants, in the context of strengthening pro-independence nationalism. These developments help explain where and how this lethal repression took place, as well as its key objectives (containment, punishment, deterrence). The late colonial authorities experienced great difficulties in spatially containing pro-independence demonstrations and urban mobility more widely.
GHB for cataplexy: Possible mode of action

The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to ‘heterologous denervation supersensitivity’ resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors (‘autoreceptors’). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the ‘switching off’ of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition.
Landing Error Scoring System Differences Between Single-Sport and Multi-Sport Female High School-Aged Athletes.

CONTEXT Single-sport specialization (SSS) is becoming more prevalent in youth athletes. Deficits in functional movement have been shown to predispose athletes to injury. It is unclear whether a link exists between SSS and the development of functional movement deficits that predispose SSS athletes to an increased risk of knee injury. OBJECTIVE To determine whether functional movement deficits exist in SSS athletes compared with multi-sport (M-S) athletes. DESIGN Cross-sectional study. SETTING Soccer practice fields. PATIENTS OR OTHER PARTICIPANTS A total of 40 (21 SSS [age = 15.05 ± 1.2 years], 19 M-S [age = 15.32 ± 1.2 years]) female high school athlete volunteers were recruited through local soccer clubs. All SSS athletes played soccer. INTERVENTION(S) Participants were grouped into 2 categories: SSS and M-S. All participants completed 3 trials of the standard Landing Error Scoring System (LESS) jump-landing task. They performed a double-legged jump from a 30-cm platform, landing on a rubber mat at a distance of half their body height. Upon landing, participants immediately performed a maximal vertical jump. MAIN OUTCOME MEASURE(S) Values were assigned to each trial using the LESS scoring criteria. We averaged the 3 scored trials and then used a Mann-Whitney U test to test for differences between groups. Participant scores from the jump-landing assessment for each group were also placed into the 4 defined LESS categories for group comparison using a Pearson χ(2) test. The α level was set a priori at . 05. RESULTS Mean scores were 6.84 ± 1.81 for the SSS group and 6.07 ± 1.93 for the M-S group. We observed no differences between groups (z = -1.44, P = .15). A Pearson χ(2) analysis revealed that the proportions of athletes classified as having excellent, good, moderate, or poor LESS scores were not different between the SSS and M-S groups ([Formula: see text] = 1.999, P = .57). CONCLUSIONS Participation in soccer alone compared with multiple sports did not affect LESS scores in adolescent female soccer players. However, the LESS scores indicated that most female adolescent athletes may be at an increased risk for knee injury, regardless of the number of sports played.
The importance of transmethylation reactions to methionine metabolism in sheep: effects of supplementation with creatine and choline

The influence of administering the methylated products choline and creatine on methionine irreversible loss rate (ILR) and recycling from homocysteine has been investigated in sheep fed close to energy and N equilibrium. Two methods to estimate methionine recycling were compared. The first involved & [U-13C& ]methionine infused as part of a labelled amino acid mixture obtained from hydrolysed algal protein. In this approach the isotope dilution of methionine with all five C atoms labelled (m+5) will represent the ILR which does not recycle through homocysteine, while that which includes molecules with C-l–C-4 labelled will allow for loss of the labelled methyl (5)-C atom and replacement by an unlabelled moiety in the remethylation of homocysteine. The second method involved a combined infusion of [l-13C]- & [S-methyl-2H3& rsqb;methionine. These two approaches gave similar data for methionine ILR which does not include label recycled to the amino acid from homocysteine but differed for recycled methionine fluxes. Consequently the two procedures differed in the calculated extent of homocysteine methylation under control conditions (6 v. 28). These extents of remethylation are within the range observed for the fed human subject, despite the fact that fewer dietary methyl groups are available for the ruminant. Using combined data from the infwions, significant depression of methionine recycling occurred in blood (P <0·05), with a similar trendfor plasma (P = 0·077), when choline plus creatine were infused. Wool growth, assessed by intradermal injection of [35S]cysteine, was not altered by supplementation with the methylated products. From changes in the label pattern of free methionine in aortal, hepatic portal and hepatic venous blood during U-13C-labelled algal hydrolysate infusion, the major sites of homocysteine remethylation appear to be the portal-drained viscera and the liver. This was confirmed by analysis of free methionine enrichments in various tissues following dual infusion of & [1J3C& ]- and & [S-methyl-2H3methionine, with the greatest activities occurring in rumen, jejunum and liver. Of the non-splanchnic tissues examined, only kidney exhibited substantial methionine cycling; none was detected in muscle, heart, lung and skin. The implications of methyl group provision under net prduction conditions are discussed.
Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial.

OBJECTIVE To determine whether chondroitin sulfate (CS) is effective in inhibiting cartilage loss in knee osteoarthritis (OA). METHODS In this randomized, double-blind, placebo-controlled trial, 300 patients with knee OA were recruited from an outpatient clinic, from private practices, and through advertisements. Study patients were randomly assigned to receive either 800 mg CS or placebo once daily for 2 years. The primary outcome was joint space loss over 2 years as assessed by a posteroanterior radiograph of the knee in flexion; secondary outcomes included pain and function. RESULTS Of 341 patients screened, 300 entered the study and were included in the intent-to-treat analysis. The 150 patients receiving placebo had progressive joint space narrowing, with a mean +/- SD joint space loss of 0.14 +/- 0.61 mm after 2 years (P = 0.001 compared with baseline). In contrast, there was no change in mean joint space width for the 150 patients receiving CS (0.00 +/- 0.53 mm; P not significant compared with baseline). Similar results were found for minimum joint space narrowing. The differences in loss of joint space between the two groups were significant for mean joint space width (0.14 +/- 0.57 mm; P = 0.04) and for minimum joint space width (0.12 +/- 0.52 mm; P = 0.05). CS was well tolerated, with no significant differences in rates of adverse events between the two groups. CONCLUSION While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.
Direct Interaction between SET8 and Proliferating Cell Nuclear Antigen Couples H4-K20 Methylation with DNA Replication*

Chromatin endowed by histone modifications governs chromatin structure, which in turn represents a means to regulate cellular processes, including transcription and heterochromatin formation. Recent evidence revealed a plethora of enzymes that catalyze specific histone modifications for epigenetic maintenance, and dysregulation of which contributes to tumorigenesis and developmental defects. The histone methyltransferase SET8 (also known as Pr-Set7) was previously reported to monomethylate Lys20 of histone H4. However, the temporal and spatial control of SET8 activity remains elusive. Here, we provide evidence to support that SET8 monomethylates Lys20 of histone H4 during S phase by tethering to proliferating cell nuclear antigen via a putative proliferating cell nuclear antigen-interacting protein box. In addition, we show that SET8 function is required for S phase progression. Finally, deletion of SET8 in mice causes embryonic lethality, suggesting that SET8 plays an important role in mammalian embryogenesis.
Changes in monocyte/macrophage neurotoxicity in the era of HAART: implications for HIV-associated dementia

Objective To determine changes in CD14/CD69 cells of HIV seropositive patients with HIV-1 associated dementia (HAD) on highly active antiretroviral therapy (HAART) and to determine the effect of soluble factors from cultured monocyte/macrophage (M/M&phis;) on neural cell functional proteins. Design and methods Whole blood from patients with HAD, HIV seronegative subjects, and HIV seropositive subjects with no dementia (HIV-ND) was analyzed for CD14/CD69 cells using flow cytometry. M/M&phis; were isolated and cultured, and supernatants tested for neurotoxicity. Modulation of neural cell proteins and mitogen-activated protein kinases in response to supernatant exposure was examined by Western blot. Results CD14/CD69 levels from HAART-treated HAD subjects were significantly elevated over those from HIV-ND subjects and controls. However, levels were significantly lower than those reported in similarly selected HAD subjects tested prior to the HAART era. Treatment of neural cells with M/M&phis;-derived culture supernatants from HAART-treated HAD subjects was not associated with cell death, but resulted in a trend towards lower activation of the JNK, AKT, and ERK kinases, decreased expression of SNAP-25, and increased expression of neurofilament light than was observed after treatment with HIV-ND M/M&phis; supernatants. Conclusions The clinical phenotype of HAD appears to be evolving from a subacute dementing disease to a more protracted disorder. Decreased CD14/CD69 levels may reflect changes in some aspects of the pathophysiology of brain injury in the era of HAART. Changes in neural cell signaling, structural and functional proteins may represent more subtle neurotoxicity, manifested in cell dysfunction rather than frank cell death.
Diabetes-Associated Mesenteric Vascular Hypertrophy Is Attenuated by Angiotensin-Converting Enzyme Inhibition

In experimental diabetes, the mesenteric vascular tree undergoes hypertrophy, and this is associated with an increase in mesenteric angiotensin-converting enzyme (ACE) levels. The aim of this study was to determine if inhibition of mesenteric ACE by ACE inhibition would influence diabetes-associated mesenteric vascular hypertrophy. Control or streptozocin-induced diabetic rats were randomized to receive no drug or the ACE inhibitor perindopril. In addition, other diabetic rats were randomized to receive either low-dose insulin that does not alter glycemic control or high-dose insulin, administered as a silastic pellet to achieve euglycemia. After 3 weeks, animals were killed for measurement of mesenteric ACE, vessel weight, and wall:lumen ratio. Diabetes was associated with increased mesenteric ACE levels, increased vessel weight, and an increase in the wall:lumen ratio. ACE inhibition, despite no effect on glycemic control, food intake, urinary urea excretion, or gut weight, prevented the increase in mesenteric ACE levels and attenuated mesenteric vascular hypertrophy as assessed by weight or wall:lumen ratio. The increase in staining by an antibody to the endothelial product, von Willebrand factor, in diabetic rats was totally prevented by perindopril treatment. Euglycemia but not low-dose insulin therapy in the diabetic rats normalized mesenteric vessel ACE, weight, and wall:lumen ratio. In conclusion, ACE inhibition may have a specific role in preventing diabetes-associated vascular hypertrophy, an important process in the genesis of micro- and macrovascular diabetic complications.
Quantifying the adsorption of ionic silver and functionalized nanoparticles during ecotoxicity testing: Test container effects and recommendations

Abstract Silver nanoparticles (Ag-NPs) are used in a wide variety of products, prompting concerns regarding their potential environmental impacts. To accurately determine the toxicity of Ag-NPs it is necessary to differentiate between the toxicity of the nanoparticles themselves and the toxicity of ionic silver (Ag) released from them. This is not a trivial task given the reactive nature of Ag in solution, and its propensity for both adsorption and photoreduction. In the experiments reported here, we quantified the loss of silver from test solutions during standard ecotoxicity testing conducted using a variety of different test container materials and geometries. This sensitive 110mAg isotope tracing method revealed a substantial underestimation of the toxicity of dissolved Ag to the green algae Pseudokirchneriella subcapitata when calculated only on the basis of the initial test concentrations. Furthermore, experiments with surface-functionalized Ag-NPs under standard algal growth inhibition test conditions also demonstrated extensive losses of Ag-NPs from the solution due to adsorption to the container walls, and the extent of loss was dependent on Ag-NP surface-functionality. These results hold important messages for researchers engaged in both environmental and human nanotoxicology testing, not only for Ag-NPs but also for other NPs with various tailored surface chemistries, where these phenomena are recognized but are also frequently disregarded in the experimental design and reporting.
The Protein Synthesis Inhibitor Blasticidin S Enters Mammalian Cells via Leucine-rich Repeat-containing Protein 8D

Background: Leucine-rich repeat-containing 8 (LRRC8) proteins are involved in lymphocyte development and adipocyte differentiation. Results: LRRC8D is required for the import of the antibiotic blasticidin S. Conclusion: LRRC8D functions as a transporter of small molecules. Significance: This suggests a mode of action for LRRC8 family members in lymphocyte development and adipocyte differentiation. Leucine-rich repeat-containing 8 (LRRC8) proteins have been identified as putative receptors involved in lymphocyte development and adipocyte differentiation. They remain poorly characterized, and no specific function has been assigned to them. There is no consensus on how this family of proteins might function because homology searches suggest that members of the LRRC8 family act not as plasma membrane receptors, but rather as channels that mediate cell-cell signaling. Here we provide experimental evidence that supports a role for LRRC8s in the transport of small molecules. We show that LRRC8D is a mammalian protein required for the import of the antibiotic blasticidin S. We characterize localization and topology of LRRC8A and LRRC8D and demonstrate that LRRC8D interacts with LRRC8A, LRRC8B, and LRRC8C. Given the suggested involvement in solute transport, our results support a model in which LRRC8s form one or more complexes that may mediate cell-cell communication by transporting small solutes.
Replication-Independent Long-Distance Trafficking by Viral RNAs in Nicotiana benthamiana[W]

Viruses with separately encapsidated genomes could have their genomes introduced into different leaves of a plant, thus necessitating long-distance trafficking of the viral RNAs for successful infection. To examine this possibility, individual or combinations of genome segments from the tripartite Brome mosaic virus (BMV) were transiently expressed in leaves of Nicotiana benthamiana plants using engineered Agrobacterium tumefaciens. BMV RNA3 was found to traffic from the initial site of expression to other leaves of the plant, as detected by RNA gel blot analyses and also by the expression of an endoplasmic reticulum–targeted green fluorescent protein. When RNA3 trafficked into leaves containing the BMV replication enzymes, RNA replication, transcription, and virion production were observed. RNA3 trafficking occurred even when it did not encode the movement or capsid proteins. However, coexpression of the movement protein increased the trafficking of BMV RNAs. BMV RNA1 and RNA2 could also traffic throughout the plant, but less efficiently than RNA3. All three BMV RNAs trafficked bidirectionally to sink leaves near the apical meristem as well as to the source leaves at the bottom of the stem, suggesting that trafficking used the phloem. These results demonstrate that BMV RNAs can use a replication-independent mechanism to traffic in N. benthamiana.
Relationship between blood lead and nutritional factors in preschool children: a cross-sectional study.

OBJECTIVE The purpose of this study was to assess the relationships between selected nutritional factors and blood lead levels of preschool children. METHODOLOGY Data on 296 children, aged 9 to 72 months, who were cared for at the University of Maryland at Baltimore Pediatric Ambulatory Center were examined in this cross-sectional study. Nutritional status, socioeconomic aspects, medical history, and potential sources of lead exposure were assessed. Blood samples were evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte photoporphyrin, calcium, and hematocrit. RESULTS The average blood lead level was 11.4 micrograms/dL. Multicollinearity of nutritional factors was addressed using regression techniques. After adjusting for confounders, significant positive associations with blood lead were found for total caloric intake (P = .01) and dietary fat (P = .05). CONCLUSIONS The findings of this study suggest that even when behavioral and environmental exposures to lead were statistically controlled, total caloric intake and dietary fat each had an independent and significant association with the level of blood lead.
The Ancient Maya Drought Cult: Late Classic Cave Use in Belize

Abstract Caves were used as ritual venues by the ancient Maya from the Early Preclassic to the Postclassic period. These sites have been intensively investigated, but little research has been devoted to changes in cave use over time. Work at Chechem Ha Cave in western Belize investigates transformations in ritual practice occurring between the Early and Late Classic periods using an explanatory framework that incorporates high-definition archaeological research with a paleoclimate reconstruction derived from speleothems. This is one of the first projects to directly link these data to the archaeological record. We also introduce new methodology to evaluate changes in ritual practice using use-intensity proxies and artifact patterning. These data demonstrate that Late Classic transformations were coeval with climatic drying. The phenomenon was identified in this case study, and the pattern is prevalent throughout the eastern lowlands suggesting that an ancient Maya drought cult was initiated at this time. We provide the first evidence that there was a failed ritual response to environmental stress, implying that a loss of faith in Maya rulership contributed to the downfall of political systems. This is an important finding for collapse theories that include ideological causations.
PAK1 Negatively Regulates the Activity of the Rho Exchange Factor NET1*

Rho family small G-protein activity is controlled by guanine nucleotide exchange factors that stimulate the release of GDP, thus allowing GTP binding. Once activated, Rho proteins control cell signaling through interactions with downstream effector proteins, leading to changes in cytoskeletal organization and gene expression. The ability of Rho family members to modulate the activity of other Rho proteins is also intrinsic to these processes. In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner. Furthermore, coexpression of constitutively active PAK1 inhibits the ability of NET1 to stimulate actin polymerization only when serines 152 and 153 are present. These data provide a novel mechanism for the control of RhoA activity by Rac1 through the PAK-dependent phosphorylation of NET1 to reduce its activity as a guanine nucleotide exchange factor.