Delivery of functional Cas:DNA nucleoprotein complexes into recipient bacteria through a type IV secretion system.

CRISPR-associated (Cas) endonucleases and their derivatives are widespread tools for the targeted genetic modification of both prokaryotic and eukaryotic genomes. A critical step of all CRISPR-Cas technologies is the delivery of the Cas endonuclease to the target cell. Here, we investigate the possibility of using bacterial conjugation to translocate Cas proteins into recipient bacteria. Conjugative relaxases are translocated through a type IV secretion system into the recipient cell, covalently attached to the transferred DNA strand. We fused relaxase R388-TrwC with the endonuclease Cas12a and confirmed that it can be transported through a T4SS. The fusion protein maintained its activity upon translocation by conjugation into the recipient cell, as evidenced by the induction of the SOS signal resulting from DNA breaks produced by the endonuclease in the recipient cell, and the detection of mutations at the target position. We further show how a template DNA provided on the transferred DNA can be used to introduce specific mutations. The guide RNA can also be encoded by the transferred DNA, enabling its production in the recipient cells where it can form a complex with the Cas nuclease transferred as a protein. This self-contained setup enables to target wild-type bacterial cells. Finally, we extended this strategy to the delivery of relaxases fused to base editors. Using TrwC and MobA relaxases as drivers, we achieved precise editing of transconjugants. Thus, conjugation provides a delivery system for Cas-derived editing tools, bypassing the need to deliver and express a cas gene in the target cells.

Neurexins: molecular codes for shaping neuronal synapses.

The function of neuronal circuits relies on the properties of individual neuronal cells and their synapses. We propose that a substantial degree of synapse formation and function is instructed by molecular codes resulting from transcriptional programmes. Recent studies on the Neurexin protein family and its ligands provide fundamental insight into how synapses are assembled and remodelled, how synaptic properties are specified and how single gene mutations associated with neurodevelopmental and psychiatric disorders might modify the operation of neuronal circuits and behaviour. In this Review, we first summarize insights into Neurexin function obtained from various model organisms. We then discuss the mechanisms and logic of the cell type-specific regulation of Neurexin isoforms, in particular at the level of alternative mRNA splicing. Finally, we propose a conceptual framework for how combinations of synaptic protein isoforms act as 'senders' and 'readers' to instruct synapse formation and the acquisition of cell type-specific and synapse-specific functional properties.

Immune and metabolic challenges induce changes in pain sensation and related pathways in the hypothalamus.

The hypothalamic molecular processes participate in the regulation of the neuro-immune-endocrine system, including hormone, metabolite, chemokine circulation, and corresponding physiological and behavioral responses. RNA-sequencing profiles were analyzed to understand the effect of juvenile immune and metabolic distress 100 days after virally elicited maternal immune activation during gestation in pigs. Over 1,300 genes exhibited significant additive or interacting effects of gestational immune activation, juvenile distress, and sex. One-third of these genes presented multiple effects, emphasizing the complex interplay of these factors. Key functional categories enriched among affected genes included sensory perception of pain, steroidogenesis, prolactin, neuropeptide, and inflammatory signaling. These categories underscore the intricate relationship between gestational immune activation during gestation, distress, and the response of hypothalamic pathways to insults. These effects were sex-dependent for many genes, such as Prdm12, Oprd1, Isg20, Prl, Oxt, and Vip. The prevalence of differentially expressed genes annotated to proinflammatory and cell cycle processes suggests potential implications for synaptic plasticity and neuronal survival. The gene profiles affected by immune activation, distress, and sex pointed to the action of transcription factors SHOX2, STAT1, and REST. These findings underscore the importance of considering sex and postnatal challenges when studying causes of neurodevelopmental disorders and highlight the complexity of the "two-hit" hypothesis in understanding their etiology. Our study furthers the understanding of the intricate molecular responses in the hypothalamus to gestational immune activation and subsequent distress, shedding light on the sex-specific effects and the potential long-lasting consequences on pain perception, neuroendocrine regulation, and inflammatory processes.NEW & NOTEWORTHY The interaction of infection during gestation and insults later in life influences the molecular mechanisms in the hypothalamus that participate in pain sensation. The response of the hypothalamic transcriptome varies between sexes and can also affect synapses and immune signals. The findings from this study assist in the identification of agonists or antagonists that can guide pretranslational studies to ameliorate the effects of gestational insults interacting with postnatal challenges on physiological or behavioral disorders.

Comparative assessment of phenotypic markers in patients with chronic inflammation: Differences on Bifidobacterium concerning liver status.

BACKGROUND: The relationship between systemic lupus erythematosus (SLE) and low-grade metabolic inflammation (MI) with the microbiota is crucial for understanding the pathogenesis of these diseases and developing effective therapeutic interventions. In this context, it has been observed that the gut microbiota plays a key role in the immune regulation and inflammation contributing to the exacerbation through inflammatory mediators. This research aimed to describe similarities/differences in anthropometric, biochemical, inflammatory, and hepatic markers as well as to examine the putative role of gut microbiota concerning two inflammatory conditions: SLE and MI. METHODS: Data were obtained from a cohort comprising adults with SLE and MI. Faecal samples were determined by 16S technique. Statistical analyses compared anthropometric and clinical variables, and LEfSe and MetagenomeSeq were used for metagenomic data. An interaction analysis was fitted to investigate associations of microbiota with fatty liver index (FLI) depending on the inflammatory condition. RESULTS: Participants with low-grade MI showed worse values in anthropometry and biochemicals compared with patients with SLE. The liver profile of patients with MI was unhealthier, while no relevant differences were found in most of the inflammatory markers between groups. LEfSe analysis revealed an overrepresentation of Bifidobacteriaceae family in SLE group. An interactive association between gut Bifidobacterium abundance and type of disease was identified for FLI values, suggesting an effect modification of the gut microbiota concerning liver markers depending on the inflammatory condition. CONCLUSION: This study found phenotypical and microbial similarities and disparities between these two inflammatory conditions, evidenced in clinical and hepatic markers, and showed the interactive interplay between gut Bifidobacterium and liver health (measured by FLI) that occur in a different manner depending on the type of inflammatory disease. These results underscore the importance of personalized approaches and individual microbiota in the screening of different inflammatory situations, considering unique hepatic and microbiota profiles.

OnabotulinumtoxinA as a promising treatment for primary trochlear headache: A retrospective case series.

OBJECTIVES: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH). METHODS: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects. RESULTS: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases. CONCLUSIONS: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management.

Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Renal Regional Oxygen Saturation and Acute Kidney Injury in Neonates with Perinatal Asphyxia.

OBJECTIVE: Neonates with moderate-to-severe perinatal asphyxia often develop acute kidney injury (AKI). Additionally, therapeutic hypothermia (TH) can affect renal blood flow. This study aimed to evaluate the association between renal regional oxygen saturation (rSrO2) during TH and AKI in neonates with moderate and severe perinatal asphyxia. STUDY DESIGN: This retrospective longitudinal study included neonates with moderate-to-severe asphyxia who required TH. The primary outcome was the occurrence of AKI, classified as a rate of decrease in creatinine levels of <33% at 72 hours of TH. rSrO2 was continuously monitored by near-infrared spectroscopy during the hypothermia and rewarming phases. Data analysis involved dividing the average rSrO2 levels into 12-hour periods. We analyzed the association between AKI and rSrO2 levels using univariate and multivariate logistic regression models. Furthermore, we assessed the predictive capacity of rSrO2 for AKI by analyzing the area under the receiver operating characteristic curve. RESULTS: Ninety-one patients were included in the study. On average, patients with AKI exhibit lower rSrO2 levels during TH. Specifically, rSrO2 levels within the first 12 hours and between 25 and 72 hours of TH demonstrated the highest predictive capability for AKI. Multivariate logistic regression analysis revealed that rSrO2 levels within the initial 12 hours (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [CI]: 1.01-1.21) and between 61 and 72 hours (aOR = 0.85, 95% CI: 0.78-0.92) were significantly associated with AKI. CONCLUSION: An increase in rSrO2 during the first 12 hours of TH and lower rSrO2 levels between 61 and 72 hours of treatment were associated with the development of AKI in asphyxiated neonates undergoing TH. KEY POINTS: · Neonates with asphyxia often develop AKI.. · Renal saturations are affected by hypothermia and asphyxia. · Patients with AKI initially show higher rSrO2, then lower rSrO2.. · Monitoring rSrO2 identifies early AKI..

Association of microscopic colitis and enteropathy due to olmesartan.

We report the case of a patient with severe chronic diarrhea. He was admitted on multiple occasions for this reason, with the cause remaining undetected. After obtaining a detailed medical history and performing several studies, the patient was diagnosed with microscopic colitis and enteropathy due to Olmesartan. In the literature, both diseases appear concurrently only in a few cases. Here we highlight the importance of conducting a comprehensive medical history and maintaining high clinical suspicion to avoid delays in the diagnosis of these uncommon pathologies, as well as unnecessary tests and empirical treatments.

Lymphocytic esophagitis - A little-known cause of dysphagia.

Lymphocytic esophagitis is a little-known entity whose cause is not fully established, and which basically presents with dysphagia. It is characterized by the presence of an infiltrate mainly formed by lymphocytes and other signs of epithelial damage in the absence of other granulocytes. The lack of knowledge about this pathology as well as standardized diagnostic criteria complicates its diagnosis. We present the case of an 84-year-old male with dysphagia and pathological findings compatible with lymphocytic esophagitis, requiring several lines of treatment and even endoscopic dilation with subsequent clinical improvement.

Primary follicular lymphoma of the duodenum as an incidental finding on upper gastrointestinal endoscopy.

Primary follicular lymphoma of the duodenum (FLD) is a rare variant of follicular lymphoma (FL), which represents only 1-4% of gastrointestinal non-hodgkin lymphomas (NHL). It usually appears in the second portion of the duodenum as micronodular lesions and the diagnosis is often incidental. Unlike other NHLs, the prognosis is excellent and the treatment ranges from "watch and wait" to rituximab-based immunochemotherapy regimens, depending on the symptoms and the presence of systemic involvement.

Association of Systemic Lupus Erythematosus Disease Activity With Choroidal Thickness.

OBJECTIVE: To determine the association between disease activity and choroidal thickness in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a cohort study of 24 SLE patients and 13 healthy controls recruited at Washington University School of Medicine between June 2019 and November 2021. SLE disease activity was assessed using the SLE Disease Activity Index-2000 Responder Index-50 (S2K RI-50). Patients were divided into four groups: high disease activity/no lupus nephritis (HDA/no LN; S2K RI-50 > 4), HDA/active LN (HDA/active LN; S2K RI-50 > 4), low disease activity/inactive LN (LDA/inactive LN; S2K RI-50 ≤ 4), and LDA/no LN (LDA/no LN; S2K RI-50 ≤ 4). LDA/no LN patients were age-, sex-, and race-matched to healthy controls and patients in other SLE groups. Choroidal thickness of the right eye was measured blinded to disease activity on a horizontal section through the fovea on optical coherence tomography images taken within a week of disease assessment. RESULTS: Patients with HDA had choroidal thickening compared with matched patients with LDA. After controlling for multiplicity, choroidal thinning remained statistically significant at 1000 µm nasal to the fovea (308 ± 68 vs 228 ± 64 µm, p = 0.001). Choroidal thickness was not different between LDA/no LN and LDA/inactive LN or healthy controls. CONCLUSION: HDA in patient with SLE is associated with increased choroidal thickness whereas comorbid inactive LN did not affect choroidal thickness. Additional studies in a larger longitudinal cohort are needed to study whether choroidal thickness may be used as a noninvasive, adjunctive measure for disease activity in SLE.

Colonization With Antibiotic-Resistant Bacteria in a Hospital and Associated Communities in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: We estimated the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) from a hospital and associated communities in western Guatemala. METHODS: Randomly selected infants, children, and adults (<1, 1-17, and ≥18 years, respectively) were enrolled from the hospital (n = 641) during the coronavirus disease 2019 (COVID-19) pandemic, March to September 2021. Community participants were enrolled using a 3-stage cluster design between November 2019 and March 2020 (phase 1, n = 381) and between July 2020 and May 2021 (phase 2, with COVID-19 pandemic restrictions, n = 538). Stool samples were streaked onto selective chromogenic agar, and a Vitek 2 instrument was used to verify ESCrE or CRE classification. Prevalence estimates were weighted to account for sampling design. RESULTS: The prevalence of colonization with ESCrE and CRE was higher among hospital patients compared to community participants (ESCrE: 67% vs 46%, P < .01; CRE: 37% vs 1%, P < .01). Hospital ESCrE colonization was higher for adults (72%) compared with children (65%) and infants (60%) (P < .05). Colonization was higher for adults (50%) than children (40%) in the community (P < .05). There was no difference in ESCrE colonization between phase 1 and 2 (45% and 47%, respectively, P > .05), although reported use of antibiotics among households declined (23% and 7%, respectively, P < .001). CONCLUSIONS: While hospitals remain foci for ESCrE and CRE colonization, consistent with the need for infection control programs, community prevalence of ESCrE in this study was high, potentially adding to colonization pressure and transmission in healthcare settings. Better understanding of transmission dynamics and age-related factors is needed.

Modulating the G-Quadruplex and Duplex DNA Binding by Controlling the Charge of Fluorescent Molecules.

Two fluorescent and non-toxic spirobifluorene molecules bearing either positive (Spiro-NMe3) or negative (Spiro-SO3) charged moieties attached to the same aromatic structure have been investigated as binders for DNA. The novel Spiro-NMe3 containing four alkylammonium substituents interacts with G-quadruplex (G4) DNA structures and shows preference for G4s over duplex by means of FRET melting and fluorescence experiments. The interaction is governed by the charged substituents of the ligands as deduced from the lower binding of the sulfonate analogue (Spiro-SO3). On the contrary, Spiro-SO3 exhibits higher binding affinity to duplex DNA structure than to G4. Both molecules show a moderate quenching of the fluorescence upon DNA binding. The confocal microscopy evaluation shows the internalization of both molecules in HeLa cells and their lysosomal accumulation.

Lrp4 is a receptor for Agrin and forms a complex with MuSK.

Neuromuscular synapse formation requires a complex exchange of signals between motor neurons and skeletal muscle fibers, leading to the accumulation of postsynaptic proteins, including acetylcholine receptors in the muscle membrane and specialized release sites, or active zones in the presynaptic nerve terminal. MuSK, a receptor tyrosine kinase that is expressed in skeletal muscle, and Agrin, a motor neuron-derived ligand that stimulates MuSK phosphorylation, play critical roles in synaptic differentiation, as synapses do not form in their absence, and mutations in MuSK or downstream effectors are a major cause of a group of neuromuscular disorders, termed congenital myasthenic syndromes (CMS). How Agrin activates MuSK and stimulates synaptic differentiation is not known and remains a fundamental gap in our understanding of signaling at neuromuscular synapses. Here, we report that Lrp4, a member of the LDLR family, is a receptor for Agrin, forms a complex with MuSK, and mediates MuSK activation by Agrin.

Dual therapy with Erenumab and onabotulinumtoxinA: No synergistic effect in chronic migraine: A retrospective cohort study.

OBJECTIVE: To assess whether dual therapy with erenumab and onabotulinumtoxinA (BoNTA) was more effective than erenumab alone in chronic migraine. BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in migraine. Erenumab binds to the canonical CGRP receptor in Aδ-fibers, and BoNTA prevents the release of CGRP from meningeal and extracranial C-fibers. It is still unknown whether dual therapy is more effective. METHODS: This was a retrospective study in a Headache Unit. There was a thorough revision of charts of patients receiving erenumab from December 2019 to March 2021. The cohort was divided into three groups according to BoNTA at the start of erenumab: (1) WBT: were on BoNTA and maintained it as dual therapy; (2) WoBT: were on BoNTA and discontinued; (3) NoBT: were not on BoNTA. Primary endpoint was reduction in monthly headache days (MHD) at 12 weeks. Secondary endpoints were percent improvement and ≥50% reduction in MHD. RESULTS: Of 237 charts reviewed, 187 met the inclusion criteria. Seventy-three (39%) were included in WBT, 44 (23.5%) in WoBT, and 70 (37.4%) in NoBT. The reduction in MHD was less with dual therapy [WBT 4.7 ± 7.68, WoBT 5.12 ± 7.98 (p = 0.80), NoBT 8.21 ± 7.84 p = 0.009]. The percentage of improvement was higher in the erenumab-alone group [NoBT 35%, WoBT 22.3% (p = 0.92), WBT 21.7% (p = 0.001)]. The probability of achieving a ≥ 50% reduction in MHD was lower in WBT than in WoBT (OR 0.66, p = 0.35) and in the NoBT group (OR 0.57, p = 0.14). CONCLUSIONS: Our findings suggest that dual therapy is less effective than erenumab alone. However, since the design has multiple limitations, further prospective studies are required to validate these data.

A case report of fatal feline babesiosis caused by Babesia canis in north western Spain.

BACKGROUND: In Europe, Babesia infections in cats are sporadic and only partial knowledge is currently available since the number of described cases including both the clinical presentation and the molecular identification of the Babesia species involved is limited. In the present case report, the clinical signs, the epidemiological data and the molecular results suggest that this is the first reported fatal case of feline babesiosis caused by Babesia canis. CASE PRESENTATION: A six month old female European shorthair cat from north-western Spain died after being hospitalized for two days. This animal was pregnant and showed anorexia, lethargy, weakness, jaundice and fever with increased respiratory and heart rates. Haematological analysis revealed haemolytic regenerative anaemia, thrombocytopenia and leukocytosis. The presence of piroplasms was assessed using a PCR targeting the 18S rRNA gene of Babesia spp. and Theileria spp.; the sample resulted positive and B. canis was identified by DNA sequence analysis. The possible existence of co-infections with other vector-borne pathogens such as Anaplasma spp., Bartonella spp., Borrelia burgdorferi s.l., Cytauxzoon spp., Ehrlichia spp., Hepatozoon canis, Mycoplasma spp. or Rickettsia spp. was excluded by qPCR. CONCLUSIONS: Our results together with previous reports on Babesia infections in cats from Europe suggest that feline babesiosis should be included in the differential diagnosis of animals with anaemia, thrombocytopenia, anorexia and lethargy, especially in young or immunocompromised animals from endemic areas for canine babesiosis.

Prediction of leptospirosis outbreaks by hydroclimatic covariates: a comparative study of statistical models.

Leptospirosis, the infectious disease caused by a spirochete bacteria, is a major public health problem worldwide. In Argentina, some regions have climatic and geographical characteristics that favor the habitat of bacteria of the Leptospira genus, whose survival strongly depends on climatic factors, enhanced by climate change, which increase the problems associated with people's health. In order to have a method to predict leptospirosis cases, in this paper, five time series forecasting methods are compared: two parametric (autoregressive integrated moving average and an alternative one that allows covariates, ARIMA and ARIMAX, respectively), two nonparametric (Nadaraya-Watson Kernel estimator, one and two kernels versions, NW-1 K and NW-2 K), and one semiparametric (semi-functional partial linear regression, SFPLR) method. For this, the number of cases of leptospirosis registered from 2009 to 2020 in three important cities of northeastern Argentina is used, as well as hydroclimatic covariates related to the presence of cases. According to the obtained results, there is no method that improves considerably the rest and can be recommended as a unique tool for leptospirosis prediction. However, in general, the NW-2 K method gets a better performance. This work, in addition to using a long-term high-quality time series, enriches the area of applications of statistical models to epidemiological leptospirosis data by the incorporation of hydroclimatic variables, and it is recommended directing further efforts in this line of research, under the context of current climate change.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns in Northeast Mexico.

OBJECTIVE: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymatic disease worldwide and the prevalence is not well established because of the lack of screening. This study aimed to estimate the prevalence of G6PDd in a Hispanic population from Northeast Mexico. STUDY DESIGN: In this retrospective study, a database was used to analyze the G6PDd in neonates included in the expanded newborn metabolic screening of inherited metabolic disorders during a period of 4 years through the GSP Neonatal G6 kit (PerkinElmer). RESULTS: Among 96,152 (48,462 male) neonates screened for G6PD enzyme activity, a total of 566 (0.58%) cases were deficient for G6PD. Of those 566 patients, 469 (82.8%) attended the second test and the other 97 (17.2%) patients were lost. Of those 469 who did attend, 384 (81.9%) neonates were deficient in the second test and 85 (18.1%) were normal. With the data collected, 384 neonates were confirmed with G6PDd, 348 (88.6%) were male and 36 (11.4%) patients were female. The calculated prevalence for this population was 0.72 cases per 100 male newborns. CONCLUSION: The prevalence of G6PDd in the Northeastern Mexican population is high. Since migration is increasing in the United States, pediatricians should be aware of the need to search for G6PDd in newborns and the wide clinical manifestations they can present. KEY POINTS: · The calculated prevalence of glucose-6-phosphate dehydrogenase deficiency in Northeast Mexico is 3.99 cases per 1,000 newborns.. · Glucose-6-phosphate dehydrogenase deficiency screenings should be included in all newborn metabolic screenings.. · Glucose-6-phosphate dehydrogenase deficiency is a common erythroenzymopathy that must be addressed as a public health concern. To anticipate clinical complications, target population monitoring is required..

The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease.

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. This review summarizes our current knowledge of the molecular aspects and cellular processes involving TIA1, with relevance for human pathophysiology.

Exploring the Impact of Maternal and Paternal Acceptance on Adolescent Girls' Emotion Regulation.

Maternal acceptance is associated with youth emotion regulation (a correlate of depression among adolescent girls); however, less is known about the impact of fathers. In this prospective study, we examined effects of maternal and paternal acceptance on youth sadness inhibition (a facet of emotion dysregulation) among adolescent girls (n = 82; Mage = 13.28; 43% from minoritized racial/ethnic groups) over 1 year. Youth varied on depression risk, which was assessed via clinical diagnostic interviews. Bivariate results showed that maternal acceptance was associated with lower youth sadness inhibition at baseline and 1-year follow-up, while paternal acceptance was only associated with lower youth sadness inhibition at 1-year follow-up. Step-wise regressions showed that paternal acceptance was inversely associated with youth sadness inhibition over time, above and beyond effects of youth age, baseline sadness inhibition, depression risk, and maternal acceptance. Findings highlight the importance of examining both mothers' and fathers' impact on adolescent girls' development of emotion regulation.