Weight Variation by Sex and Nature of Risk Factors in High-Risk Infants: An Evolutionary Perspective

A retrospective cohort study was conducted to explore growth variation during the intrauterine and early postnatal period by sex and nature of high-risk factors (i.e. physiological and pathological) in 831 Korean infants at a University hospital. The results showed that infants with a physiological risk showed a more congruent intrauterine growth pattern compared to those with a pathological risk. Particularly with a physiological risk, female infants experienced more compatible intrauterine and postnatal growth than males, although male infants were heavier than female infants at a given gestational age. In conclusion bigger may not necessarily be better for prenatal growth in humans. A more confluent intrauterine growth in infants with physiological risk can be beneficial for early postnatal catch-up growth. From an evolutionary perspective, female infants with a physiological risk may keep their advantageous edge over male infants during the early postnatal period although such an advantage may not be present with a pathological condition

Paul Thornell Baker (1927-2007)

Paul Thornell Baker, Evan Pugh Professor Emeritus of Anthropology at the Pennsylvania State University died on Thursday, November 29, 2007, at the age of 80 after a long illness. He is survived by his wife of fifty-eight years, Thelma Shoher Baker of Chapel Hill, North Carolina; his son, Joshua Baker of Hillsborough, NC; his daughters, Deoborah Baker of San Francisco, CA; Amy Carter of Minneapolis, MN; Felicia LeClere of Granger, IN; as well as nine grandchildren

Weight Variation by Sex and Nature of Risk Factors in High-Risk Infants: An Evolutionary Perspective

A retrospective cohort study was conducted to explore growth variation during the intrauterine and early postnatal period by sex and nature of high-risk factors (i.e. physiological and pathological) in 831 Korean infants at a University hospital. The results showed that infants with a physiological risk showed a more congruent intrauterine growth pattern compared to those with a pathological risk. Particularly with a physiological risk, female infants experienced more compatible intrauterine and postnatal growth than males, although male infants were heavier than female infants at a given gestational age. In conclusion bigger may not necessarily be better for prenatal growth in humans. A more confluent intrauterine growth in infants with physiological risk can be beneficial for early postnatal catch-up growth. From an evolutionary perspective, female infants with a physiological risk may keep their advantageous edge over male infants during the early postnatal period although such an advantage may not be present with a pathological condition

Environmental Stress and Adaptational Responses: Consequences for Human Health Outcomes

With the dramatic pace of modernization of the world’s population, human adaptation as a theoretical construct and paradigm will likely become a focal scientific issue involving scientists from many disciplinary areas during the 21st Century. Macro and micro environments are in rapid flux and human populations are exposed to rapid change. The concept of adaptation, at least in the field of biological anthropology and human biology, will likely remain tied to evolutionary processes and concepts of selection and fitness. In this paper, we discuss the theoretical constructs of adaptation and adaptability and select three current examples from our ongoing research that involve studies of adaptation and evolutionary processes in modernizing populations in different locations worldwide

Outer Surface Protein C Typing of Borrelia burgdorferi in the Tick Populations of the Upper Susquehanna River Basin, New York

Lyme disease, the most common zoonotic disease in the United States, is caused by the spirochete Borrelia burgdorferi. In order to manage and confront the notable rise in Lyme disease cases, it is crucial to cultivate a deeper understanding of B. burgdorferi and its genes. The outer surface protein C (ospC) gene is highly polymorphic and commonly used as a genetic marker due to its crucial role in establishing mammalian infection. We report novel data on the prevalence of B. burgdorferi ospC genotypes in the infected tick populations of the Upper Susquehanna River Basin of New York State. DNA extracted from 266 Ixodes scapularis, the blacklegged ticks, were tested for the presence of ospC gene and the positive samples were subjected to sequencing. The specific ospC genotype was identified for 56 positive samples which were infected with B. burgdorferi representing a single ospC genotype. A total of 12 ospC genotypes were identified in the 56 ticks, with genotypes I, K, and A being the most prevalent across the Upper Susquehanna River Basin with little variation among the six counties. The frequency distribution of ospC variants in this region is significantly different from the few previously studied regions in the Northeast. This research will have implications in the public health sector by providing assessment for Lyme disease risk in the Upper Susquehanna River Basin and insight into strain specific vaccines based on OspC. Further research can be done into the dispersion pattern of B. burgdorferi within the Upper Susquehanna River Basin, while also replicating this study for other regions

Behavioral and Environmental Residential Risk Factors for Lyme Disease in the Southern Tier of New York

During the past 40 years, Lyme disease has emerged as the most widely reported vector-borne illness in the U.S., with the majority of cases occurring in the Northeastern United States. The pathogenic bacterium Borrelia burgdorferi relies on the deer tick, Ixodes scapularis, the primary enzootic vector responsible for the passage of the bacteria to humans. Behavioral risk factors for tick-borne diseases include those that increase the likelihood of being bit by a tick, including contact with vegetation, exposed skin, and spending time outdoors, all of which can occur within one’s residential yard. Risk factors within the assumed safety net of the home have not been extensively studied, nor has the effects of pet ownership, nor the presence of wild animals within the yard. During 2019-2020 we conducted 130 surveys of households in Broome and Chenango Counties, and performed tick drags in the rear yards of 102 of these homes. Risk factors included household members’ time spent in yard, type of outside activity, use of tick control methods, seasonal activity, and pet ownership, as well as specifics of the yard, including amount and type of vegetation and presence of wild animals. The household’s history of tick bites and infection were also recorded. A risk analysis is currently underway to determine which factors contribute to a higher risk of contracting tick-borne illnesses. This study is part of our ongoing effort to understand the threat of tick-borne diseases in peri-urban and urban settings within the Southern Tier of New York.https://orb.binghamton.edu/research_days_posters_2022/1034/thumbnail.jp

TDP-43/FUS in motor neuron disease: complexity and challenges

Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their nuclear clearance and simultaneous cytoplasmic aggregation in affected motor neurons. Since the discoveries in the last decade implicating TDP-43 and FUS toxicity in ALS, a majority of studies have focused on their cytoplasmic aggregation and disruption of their RNA-binding functions. However, TDP-43 and FUS also bind to DNA, although the significance of their DNA binding in disease-affected neurons has been less investigated. A recent observation of accumulated genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal DNA damage repair pathways indicate a possible role of deregulated DNA binding function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS disease subtypes, crosstalk of etiopathologies in disease progression, available animal models and their limitations, and recent advances in understanding the specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron diseases.Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear. One unique feature of TDP-43 and FUS pathogenesis in ALS is their nuclear clearance and simultaneous cytoplasmic aggregation in affected motor neurons. Since the discoveries in the last decade implicating TDP-43 and FUS toxicity in ALS, a majority of studies have focused on their cytoplasmic aggregation and disruption of their RNA-binding functions. However, TDP-43 and FUS also bind to DNA, although the significance of their DNA binding in disease-affected neurons has been less investigated. A recent observation of accumulated genomic damage in TDP-43 and FUS-linked ALS and association of FUS with neuronal DNA damage repair pathways indicate a possible role of deregulated DNA binding function of TDP-43 and FUS in ALS. In this review, we discuss the different ALS disease subtypes, crosstalk of etiopathologies in disease progression, available animal models and their limitations, and recent advances in understanding the specific involvement of RNA/DNA binding proteins, TDP-43 and FUS, in motor neuron diseases

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease

<p>Abstract</p> <p>Background</p> <p>The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD.</p> <p>Methods</p> <p>Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years.</p> <p>Results</p> <p>Our results indicate two types of risks for those who attended the feast, a <it>Feast Risk </it>and a G<it>eneral Risk</it>. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing.</p> <p>Conclusion</p> <p>The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans.</p

Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects

Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is characteristically observed in spinal motor neurons. While emerging evidence suggests involvement of other RNA/DNA binding proteins, like FUS in DNA damage response (DDR), the role of TDP-43 in DDR has not been investigated. Here, we report that TDP-43 is a critical component of the nonhomologous end joining (NHEJ)-mediated DNA double-strand break (DSB) repair pathway. TDP-43 is rapidly recruited at DSB sites to stably interact with DDR and NHEJ factors, specifically acting as a scaffold for the recruitment of break-sealing XRCC4-DNA ligase 4 complex at DSB sites in induced pluripotent stem cell-derived motor neurons. shRNA or CRISPR/Cas9-mediated conditional depletion of TDP-43 markedly increases accumulation of genomic DSBs by impairing NHEJ repair, and thereby, sensitizing neurons to DSB stress. Finally, TDP-43 pathology strongly correlates with DSB repair defects, and damage accumulation in the neuronal genomes of sporadic ALS patients and in Caenorhabditis elegans mutant with TDP-1 loss-of-function. Our findings thus link TDP-43 pathology to impaired DSB repair and persistent DDR signaling in motor neuron disease, and suggest that DSB repair-targeted therapies may ameliorate TDP-43 toxicity-induced genome instability in motor neuron disease.Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is characteristically observed in spinal motor neurons. While emerging evidence suggests involvement of other RNA/DNA binding proteins, like FUS in DNA damage response (DDR), the role of TDP-43 in DDR has not been investigated. Here, we report that TDP-43 is a critical component of the nonhomologous end joining (NHEJ)-mediated DNA double-strand break (DSB) repair pathway. TDP-43 is rapidly recruited at DSB sites to stably interact with DDR and NHEJ factors, specifically acting as a scaffold for the recruitment of break-sealing XRCC4-DNA ligase 4 complex at DSB sites in induced pluripotent stem cell-derived motor neurons. shRNA or CRISPR/Cas9-mediated conditional depletion of TDP-43 markedly increases accumulation of genomic DSBs by impairing NHEJ repair, and thereby, sensitizing neurons to DSB stress. Finally, TDP-43 pathology strongly correlates with DSB repair defects, and damage accumulation in the neuronal genomes of sporadic ALS patients and in Caenorhabditis elegans mutant with TDP-1 loss-of-function. Our findings thus link TDP-43 pathology to impaired DSB repair and persistent DDR signaling in motor neuron disease, and suggest that DSB repair-targeted therapies may ameliorate TDP-43 toxicity-induced genome instability in motor neuron disease