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Healthy family functioning: a cross-cultural appraisal.

It is increasingly recognized that rapid cultural, social, economic, and technological changes are imposing increasing stress on family structures, traditional values, and the ability to adapt to new environments in different societies. For the purposes of this paper, "healthy family functioning" is defined in terms of a family unit (however it is conceived in any given culture) effectively coping with cultural, environmental, psychosocial, and socioeconomic stresses throughout the family life cycle. While a review of international literature in the behavioural and biomedical sciences yields little data on comparative studies, there is growing awareness of the need for cooperative international research on family coping mechanisms and determinants of self-reliant communal coping behaviour, as well as more efficient utilization of already available knowledge. After consideration of methodological pitfalls of assessment procedures, there is a presentation of an evolving theory of healthy family functioning with the suggestion that studies of young married couples constitute a particularly promising vehicle for developing needed cooperative cross-cultural research.

Cross-Cultural Comparison

Family functioning and psychiatric outcomes in children and young people with intellectual and developmental disabilities caused by rare genetic mutations.

BACKGROUND: A range of rare chromosomal micro-deletions or -duplications (Copy Number Variants - CNVs) are associated with high risk of neurodevelopmental and mental health conditions (ND-CNVs). There is great individual variability in outcomes, but we lack insights into the contributing social factors, including family functioning. METHODS: Caregivers of 598 children and young people (CYP) with a range of 16 ND-CNVs and 222 siblings without ND-CNVs (controls) completed questionnaires on overall family climate (cohesion and conflict) as well as caregiver-CYP relationship warmth and hostility and took part in a research diagnostic interview about CYPs' psychiatric symptoms. CYPs' intelligence quotient (IQ) was also measured. RESULTS: Comparisons with published data from neurotypical families indicated that families affected by ND-CNVs are characterised by higher family cohesion and conflict as well as lower caregiver-CYP warmth and hostility. Symptoms of oppositional defiant disorder reduced more steeply in CYP with ND-CNVs compared to controls with increasing family cohesion (interaction effect: β = -0.14, p = 4.65 × 10-2). In contrast, they rose more steeply with increasing family conflict (interaction effect: β = 0.18, p = 1.05 × 10-2). Furthermore, symptoms of mood disorder increased more steeply with increased caregiver-CYP hostility in CYP with ND-CNVs (interaction effect: β = 0.15, p = 4.55 × 10-2). CONCLUSIONS: Raising a CYP with a rare genetic condition is challenging. Timely access to interventions that support caregivers in fostering a positive family environment may reduce behavioural difficulties in CYP, with subsequent benefits for family functioning.

CNV

Genome-Wide Identification of the Soybean GH5 Gene Family and Functional Analysis of GmGH5-22 in Salt Tolerance.

Plant GH5 family genes function in both cell wall biosynthesis and stress responses. However, comprehensive studies on GH5 genes in the soybean remain limited. Here, we identified 28 GmGH5 genes from the soybean genome. Phylogenetic analysis assigned these genes to three subfamilies (I-III), with no representatives in subfamily IV. The GmGH5 family harbors 15 conserved motifs, which are largely similar within subfamilies but differ across subfamilies. Additionally, exon-intron structures (2-7 introns) exhibit clade-specific patterns, with members within the same clade sharing similar intron numbers and lengths, whereas distinct clades show some variation. The promoter regions of GmGH5 genes contained various cis-acting regulatory elements associated with stress responses and developmental processes. Transcriptome-based expression profiling revealed distinct tissue-specific expression patterns of GmGH5 genes. RT-qPCR further confirmed their differential expression under salt, alkaline, cold, and drought stresses, especially a significant increase in GmGH5-22 expression under salt stress (approximately 22-fold at 6 h, **** p < 0.0001). Furthermore, GmGH5-22 was highly expressed in roots, and transient expression in tobacco leaves showed its peripheral localization, which aligns with its predicted extracellular localization, suggesting that GmGH5-22 is highly likely localized to the cell wall. Overexpression of GmGH5-22 in soybean hairy roots significantly improved tolerance to salt stress. These findings establish a foundation for functional characterization of GmGH5 genes and provide viable targets for molecular breeding to enhance salt tolerance in soybeans.

GH5 family

The family as a system in hospital-based social work.

Caring for disabled family members at home can create stress that may exacerbate existing dysfunctions in the family. By changing the orientation of hospital-based social work from "disabled family member as burden" to "family unit as an ongoing system," the authors have succeeded in helping dysfunctional, disunited families become functional family systems.

Child

Diverse evolutionary rates and gene duplication patterns among families of functional olfactory receptor genes in humans.

In humans, odors are detected by ~400 functional olfactory receptor (OR) genes. The superfamily of functional OR genes can be further divided into tens of families. In large part, the OR genes have experienced extensive tandem duplications, which have led to gene gains and losses. However, whether different OR gene families have experienced distinct modes of gene duplication has yet to be reported. We conducted comparative genomic and evolutionary analyses for human functional OR genes. Based on analysis of human-mouse 1-1 orthologs, we found that human functional OR genes show higher-than-average evolutionary rates, and there are significant differences among families of functional OR genes. Via comparison with seven vertebrate outgroups, families of human functional OR genes show different extents of gene synteny conservation. Although the superfamily of human functional OR genes is enriched in tandem and proximal duplications, there are particular families which are enriched in segmental duplications. These findings suggest that human functional OR genes may be governed by different evolutionary mechanisms and that large-scale gene duplications have contributed to the early evolution of human functional OR genes.

Humans

Psychosocial status of patients randomly assigned to medical or surgical therapy for chronic stable angina.

Aspects of social and psychologic functioning are compared for 51 patients randomly assigned to surgical or medical management of chronic stable angina. No differences were found between the two groups in work status, social activity, adequacy of family functioning, perceived health, life satisfaction, memory span, extent of anxiety, hypochondriasis and hysteria. However, surgically treated patients were significantly less depressed and more likely to report improvement in health and family functioning after the initiation of treatment. It is concluded that the psychologic and social outcomes appear slightly more favorable in patients treated surgically than in those treated medically.

Adult

Genome-Wide Characterization of the Apple HD-Zip IV Gene Family and Functional Validation of MdHDZIV3 Under PEG-Induced Osmotic Stress.

The homeodomain-leucine zipper IV (HD-Zip IV) transcription factor subfamily plays essential roles in epidermal development, cuticle formation, lipid metabolism, and environmental adaptation in plants. Despite its biological importance, the HD-Zip IV family has not been systematically characterized in apple (Malus domestica). Here, we identified 17 apple HD-Zip IV genes and named them MdHDZIV1-MdHDZIV17 based on their locations on the chromosomes. The 17 genes showed a nonuniform distribution on eight chromosomes, while the occurrence of both tandem and segmental duplications indicated that family expansion involved more than one duplication mechanism. All MdHDZIV proteins contained the conserved HD, LZ, START, and SAD domains but lacked the MEKHLA domain, consistent with typical HD-Zip IV structural features. Phylogenetic analysis classified MdHDZIV proteins into five groups together with HD-Zip IV members from Arabidopsis thaliana and rice, indicating evolutionary conservation of this subfamily. Collinearity and Ka/Ks analyses revealed that duplicated MdHDZIV gene pairs were mainly subjected to purifying selection. Promoter scanning revealed diverse cis-regulatory motifs associated with hormonal signaling, environmental stress, light response, and epidermal regulation, including ABRE, ARE, W-box, MYC, G-box, and L1-box motifs. Integration of transcriptomic profiling with qRT-PCR validation revealed pronounced tissue-dependent differences in the expression of MdHDZIV genes in leaf, fruit skin, and branch bark. Under PEG6000-induced osmotic stress and NaCl-induced salt stress, 10 candidate MdHDZIV genes displayed gene-specific and stress type-specific expression patterns, with MdHDZIV3 showing strong induction under PEG6000 treatment. Functional validation in apple calli showed that MdHDZIV3 overexpression enhanced PEG tolerance, increased fresh weight, elevated SOD and POD activities, and reduced MDA accumulation under osmotic stress. These findings provide a genome-wide framework for understanding the apple HD-Zip IV gene family.

abiotic stress

'Sawa Aqwa' (Stronger Together): A multi-site randomized controlled trial of a brief family systemic intervention for adolescent mental health in Lebanon.

BACKGROUND: There are no evaluated family-based mental health and psychosocial support (MHPSS) interventions for adolescents in Southwest Asia (known as the Middle East), and few whole-family interventions in low- and middle-income countries, despite consistent evidence for the impact of family support on mental health and well-being. This study aims to evaluate the effectiveness of a brief family systemic mental health intervention, deliverable by non-specialists in mental health. METHODS: We conducted an assessor-blind type I hybrid effectiveness-implementation multi-site randomized controlled trial comparing the locally developed family intervention to a waitlist control group for randomly allocated families residing in North Lebanon and Beqa'a governorates. Eligible families presented with medium-to-high risk for child protection concerns (abuse, neglect, child labor, early marriage) and had at least one adolescent aged 12-17 who demonstrated psychological distress. Outcomes at the family, caregiver, and adolescent level were measured pre- and post-intervention, and at 3-month follow-up. RESULTS: Intent-to-treat analyses found a significant between-group effect of the intervention on adolescent-reported family functioning, caregiver mental health, and parenting. No change was found for adolescent psychological distress. Further analyses found effects on adolescent well-being for those who completed the intervention, and that father attendance was associated with better outcomes for adolescent well-being in the intervention group. No other significant moderators were found. At the 3-month follow-up for the intervention condition, family functioning and caregiver well-being significantly dropped from endline. CONCLUSIONS: The study demonstrates mixed results for a non-specialist-delivered family-systemic intervention developed in the context of humanitarian crises in Lebanon. While the intervention did not result in benefits in adolescent-reported symptoms of psychological distress, the intervention group did show greater improvements than the control group on a number of other outcomes, showing the potential impact of working with the wider family system to support adolescents in humanitarian settings.

Humans

Monocyte function in familial Mediterranean fever.

Monocytes derived from the peripheral blood of patients with familial Mediterranean fever (FMF) demonstrated a consistently lower phagocytic capacity (38-44%) for 125I-labelled Shigella flexneri when compared to monocytes from healthy subjects. Phagocytosis of both viable and killed Staphylococcus albus was similar in patients and controls. However, FMF monocytes had a two- to eight-fold depressed bactericidal capacity against S. albus in comparison to normal monocytes. Acid phosphatase and beta-glucuronidase monocyte activities were similar in patients and controls. It is suggested that the defects in monocyte function may be of importance in the pathogenesis of FMF. Colchicine had no effect on any of the indices studied.

Adolescent

Decrypting noncoding RNA interactions, structures, and functional networks.

The world of noncoding RNAs (ncRNAs) is composed of an enormous and growing number of transcripts, ranging in length from tens of bases to tens of kilobases, involved in all biological processes and altered in expression and/or function in many types of human disorders. The premise of this review is the concept that ncRNAs, like many large proteins, have a multidomain architecture that organizes them spatially and functionally. As ncRNAs are beginning to be imprecisely classified into functional families, we review here how their structural properties might inform their functions with focus on structural architecture-function relationships. We will describe the properties of "interactor elements" (IEs) involved in direct physical interaction with nucleic acids, proteins, or lipids and of "structural elements" (SEs) directing their wiring within the "ncRNA interactor networks" through the emergence of secondary and/or tertiary structures. We suggest that spectrums of "letters" (ncRNA elements) are assembled into "words" (ncRNA domains) that are further organized into "phrases" (complete ncRNA structures) with functional meaning (signaling output) through complex "sentences" (the ncRNA interactor networks). This semiotic analogy can guide the exploitation of ncRNAs as new therapeutic targets through the development of IE-blockers and/or SE-lockers that will change the interactor partners' spectrum of proteins, RNAs, DNAs, or lipids and consequently influence disease phenotypes.

DNA

How not to be seen: predicting unseen enzyme functions using contrastive learning.

MOTIVATION: Predicting enzyme function from its sequence is still an unsolved problem in the life sciences. Moreover, with the explosion of annotated genome data, we are inundated with potential enzymatic sequences that have not yet been biochemically characterized. While it is not possible to assign a not-yet-existing label to such a sequence, there is high value in placing the sequence as accurately as possible in known function space. Doing so can help provide more accurate falsifiable hypotheses for experimentalists wishing to characterize enzymes from specific functional families. RESULTS: Here we present a contrastive learning algorithm for predicting enzyme function from sequence. Our method, EnzPlacer, predicts the third, second, and first EC numbers for a protein whose fourth EC number is not in the training corpus. This novel prediction mechanism accurately places a protein sequence within a narrowed-down functional context, even if the precise function remains unknown. AVAILABILITY AND IMPLEMENTATION: EnzPlacer and data is available at https://github.com/drxiangma/EnzPlacer under a GPL3 license.

Enzymes

How Not to be Seen: Predicting Unseen Enzyme Functions using Contrastive Learning.

MOTIVATION: Predicting enzyme function from its sequence is still an unsolved problem in the life sciences. Moreover, with the explosion of annotated genome data, we are inundated with potential enzymatic sequences that have not yet been biochemically characterized. While it is not possible to assign a not-yet-existing label to such a sequence, there is high value in placing the sequence as accurately as possible in known function space. Doing so can help provide more accurate falsifiable hypotheses for experimentalists wishing to characterize enzymes from specific functional families. RESULTS: Here we present a contrastive learning algorithm for predicting enzyme function from sequence. Our method, EnzPlacer, predicts the third, second, and first EC numbers for a protein whose fourth EC number is not in the training corpus. This novel prediction mechanism accurately places a protein sequence within a narrowed-down functional context, even if the precise function remains unknown. AVAILABILITY: EnzPlacer is available from https://github.com/drxiangma/EnzPlacer under a GPL3 license.

Contrastive learning

Peripheral Macular Endothelial Dystrophy: Clinical, Histopathologic, Genetic and Functional Characterization.

OBJECTIVE: To report a CHST6-associated corneal endothelial dystrophy. DESIGN: Prospective observational case series. PARTICIPANTS: Thirty-five individuals from seven families, including 13 affected individuals exhibiting corneal epithelial and stromal edema, peripheral posterior corneal macular opacities, and endothelial guttae, as well as 22 unaffected family members. METHODS: Whole-exome sequencing was performed in 3 families and Sanger sequencing of CHST6 was performed in all individuals. Histological examination of Descemet membrane (DM) excised at the time of endothelial keratoplasty was performed for three probands. Serum keratan sulfate (KS) levels were measured in members of six families. Functional analysis of identified mutations was performed using CHST6 promoter containing CHST6 expression vector in human keratocytes (HK) and corneal endothelial cells (HCEnC). MAIN OUTCOME MEASURES: Clinical phenotype; genetic analysis; functional analysis of identified CHST6 mutations; serum KS levels; histologic examinations of DM. RESULTS: All affected individuals demonstrated peripheral macular opacities at the level of DM. Visually significant corneal edema in affected individuals was successfully managed by endothelial keratoplasty. Genetic analysis demonstrated a rare CHST6 promoter mutation (c.-690G>C) in the homozygous state in affected individuals from three families and in the compound heterozygous state with a CHST6 coding mutation (p.R211Q, p.Y268C or p.P280L) in affected individuals from the other four families. In silico analysis predicted c.-690G>C to be a regulatory variant, located at the RNA polymerase II binding site. Functional analysis in vitro demonstrated that c.-690G>C leads to increased KS sulfation in the corneal endothelium and DM, with no change of KS sulfation in keratocytes. Histologic examination of DM from affected individuals revealed elevated levels of sulfated and non-sulfated KS in DM and endothelium, consistent with the functional analysis. Minimum changes in serum sulfated KS levels were observed in affected individuals. CONCLUSIONS: We suggest the name Peripheral macular endothelial dystrophy (PMED) to describe this dystrophy that is characterized by peripheral posterior corneal macular opacities and endothelial dysfunction without stromal haze or opacities. Given that both PMED and macular corneal dystrophy are associated with promoter and coding region mutations in CHST6, we propose that they be categorized as CHST6-associated corneal dystrophies.

Humans

Comparison of quality of life in children with posterior urethral valves, isolated hydronephrosis and minor urologic conditions.

OBJECTIVE: To compare the quality of life (QoL) and family impact scores of children with posterior urethral valves (PUV), isolated hydronephrosis (HN), and those with minor urologic conditions, referred to here as minor urologic controls (MUC). METHODS: From December 2022 to April 2025, the PedsQL Inventory and Family Impact Module (FIM) questionnaires were distributed to patients in dedicated PUV, HN, and community-based urology clinics. Higher scores indicate better QoL. Children &#x2265;8 years self-completed the questionnaires, while parents served as proxies for younger children. PUV patients were compared to HN patients and MUC. RESULTS: A total of 331 patients were included (124 PUV, 101 HN, and 106 MUC). The median age differed across groups, with HN patients being the youngest (median: 7 months), followed by MUC patients (median: 36 months) and PUV patients (median: 79.5 months). Overall, PUV patients scored similarly to HN patients and MUC in QoL and FIM scores. When stratified by age, however, PUV patients <2 years old had lower median scores in total QoL, psychosocial, and family functioning domains compared to other groups. CONCLUSION: Overall, PUV was not associated with lower QoL or family impact scores compared to comparator groups in this tertiary-care cohort; however, lower scores were observed among younger children with PUV, likely reflecting parent-perceived burden early in the disease course. This highlights the importance of age-tailored support and close monitoring, particularly for younger children and families navigating early post-diagnosis care.

Humans

The proneural proteins Atonal and Scute regulate neural target genes through different E-box binding sites.

For a particular functional family of basic helix-loop-helix (bHLH) transcription factors, there is ample evidence that different factors regulate different target genes but little idea of how these different target genes are distinguished. We investigated the contribution of DNA binding site differences to the specificities of two functionally related proneural bHLH transcription factors required for the genesis of Drosophila sense organ precursors (Atonal and Scute). We show that the proneural target gene, Bearded, is regulated by both Scute and Atonal via distinct E-box consensus binding sites. By comparing with other Ato-dependent enhancer sequences, we define an Ato-specific binding consensus that differs from the previously defined Scute-specific E-box consensus, thereby defining distinct E(Ato) and E(Sc) sites. These E-box variants are crucial for function. First, tandem repeats of 20-bp sequences containing E(Ato) and E(Sc) sites are sufficient to confer Atonal- and Scute-specific expression patterns, respectively, on a reporter gene in vivo. Second, interchanging E(Ato) and E(Sc) sites within enhancers almost abolishes enhancer activity. While the latter finding shows that enhancer context is also important in defining how proneural proteins interact with these sites, it is clear that differential utilization of DNA binding sites underlies proneural protein specificity.

3' Flanking Region