Levels and trends in sex ratio at birth in provinces of Pakistan from 1980 to 2020 with scenario-based missing female birth projections to 2050: a Bayesian modeling approach

BACKGROUND: Pakistan has a strong preference for boys over girls; previous evidence on sex preference is primarily reported at the postnatal stage in which the child mortality rate is higher for females than males. Prenatal sex discrimination in Pakistan, reflected in the inflated sex ratio at birth (SRB; ratio of male to female births) has been barely mentioned before this study.OBJECTIVE: We estimate the SRB and missing female births in Pakistan provinces from 1980 to 2020 and identify provinces with imbalanced SRB. We provide scenario-based projections of missing female births in provinces without the existing SRB inflation.METHODS: An extensive SRB database of 832,091 birth records was compiled from all available surveys and censuses. To synthesize different data sources and provide annual estimates and their associated uncertainties of SRBs across provinces, we adopted a Bayesian hierarchical time series model.RESULTS: As per our model, Balochistan has had SRB imbalance since 1980. The maximum SRB was estimated as 1.121 (95% credible interval [1.066; 1.142]) in 1997. Assuming different start year of SRB inflation process in provinces without existing imbalance, the largest female birth deficit is projected to be 76.2 thousand in Punjab in 2033 when the SRB inflation starts in 2021.CONTRIBUTION: This is the first study on estimating the SRB from 1980 to 2020 and providing scenario-based projections of missing female births up to 2050 by Pakistan province. We identified the Balochistan province with imbalanced SRB and demonstrated important disparities in the occurrence and quantity of female birth deficits before 2050.

Identification of Cilia in Different Mouse Tissues

Cilia are microtubule-based hair-like organelles that extend from the cell surface. However, the existence and distribution of cilia in each organ and tissue at the postnatal stage in vivo remain largely unknown. In this study, we defined cilia distribution and arrangement and measured the ciliary lengths and the percentage of ciliated cells in different organs and tissues in vivo by using cilium dual reporter-expressing transgenic mice. Cilia were identified by the presence of ARL13B with an mCherry+ signal, and the cilium basal body was identified by the presence of Centrin2 with a GFP+ signal. Here, we provide in vivo evidence that chondrocytes and cells throughout bones have cilia. Most importantly, we reveal that: 1. primary cilia are present in hepatocytes; 2. no cilia but many centrioles are distributed on the apical cell surface in the gallbladder, intestine, and thyroid epithelia; 3. cilia on the cerebral cortex are well oriented, pointing to the center of the brain; 4. ARL13B+ inclusion is evident in the thyroid and islets of Langerhans; and 5. approximately 2% of cilia show irregular movement in nucleus pulposus extracellular fluid. This study reveals the existence and distribution of cilia and centrioles in different tissues and organs, and provides new insights for further comprehensive study of ciliary function in these organs and tissues.

Short-term supplementation of DHA as phospholipids rather than triglycerides improve cognitive deficits induced by maternal omega-3 PUFA deficiency during the late postnatal stage

Cognitive deficiencies caused by maternal omega-3 PUFA deficiency (O-3 Def), are easier reversed when supplementation of DHA as phospholipids than triglycerides, especially during the late postnatal stage.

Microbiota control of maternal behavior regulates early postnatal growth of offspring

Maternal behavior is necessary for optimal development and growth of offspring. The intestinal microbiota has emerged as a critical regulator of growth and development in the early postnatal period life. Here, we describe the identification of an intestinal Escherichia coli strain that is pathogenic to the maternal-offspring system during the early postnatal stage of life and results in growth stunting of the offspring. However, rather than having a direct pathogenic effect on the infant, we found that this particular E. coli strain was pathogenic to the dams by interfering with the maturation of maternal behavior. This resulted in malnourishment of the pups and impaired insulin-like growth factor 1 (IGF-1) signaling, leading to the consequential stunted growth. Our work provides a new understanding of how the microbiota regulates postnatal growth and an additional variable that must be considered when studying the regulation of maternal behavior.

Microbiota control of maternal behavior regulates early postnatal growth of offspring

Maternal-offspring bonding and maturation of maternal behavior is necessary during the early postnatal period of an infant to promote optimal development and growth. The regulation of maternal behavior is multifactorial relying both on sensory cues including auditory and olfactory signals emitted by the infant and received by the mother, as well as proper neuroendocrine responses including that of the oxytocin system. The intestinal microbiota has emerged as a critical regulator of growth and development in the early postnatal period of an individual’s life. While, this is best appreciated in the context of direct interactions between the microbiota and the infant, the microbiota can indirectly influence postnatal growth and development by regulating maternal factors. Here, we describe the identification of an intestinal E. coli strain that is pathogenic to the maternal-offspring system during the early postnatal stage of life and results in growth stunting of the offspring. However, rather than having a direct pathogenic effect on the infant, we found that this particular E. coli strain was pathogenic to the dams by interfering with the maturation of maternal behavior. The poor maternal behavior resulted in malnourishment of the pups and impaired IGF-1 signaling leading to the consequential stunted growth. Our work provides a new understanding of how the microbiota regulates postnatal growth and an additional variable that must be considered when studying the regulation of maternal behavior.

Effects of early-life lactoferrin intervention on growth performance, small intestinal function and gut microbiota in suckling piglets

The early postnatal stage is a critical period for suckling animals in developing intestinal function and stabilizing gut microbiota.

DAZL is a master translational regulator of murine spermatogenesis

Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3′-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

DAZL is a master translational regulator of murine spermatogenesis

Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells and essential for embryonic germ cell development and differentiation, yet gametogenic function of DAZL has not been fully characterized with most of its in vivo direct targets unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells (SSCs), meiotic arrest and spermatid arrest respectively. Using the genome-wide HITS-CLIP and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at 3′ UnTranslated Region (3′ UTR) and interacted with translation proteins including PABP. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts were significantly decreased, resulting in drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.